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J. Stephen McDaniel, M.D., Chair
Larry Brown, M.D.
Francine Cournos, M.D.
Marshall Forstein, M.D.
Karl Goodkin, M.D., Ph.D.
Constantine Lyketsos, M.D., M.H.S.
Joyce Y. Chung, M.D. (Consultant)
Originally published in November 2000. A guideline watch, summarizing significant developments in the scientific literature since publication of this guideline, may be available.
This practice guideline seeks to summarize data and specific
forms of treatment regarding the care of patients with HIV/AIDS.
The purpose of this guideline is to assist the psychiatrist in caring for
a patient with HIV/AIDS.
Psychiatrists care for patients with HIV/AIDS in
many different settings and serve a variety of functions. In many
cases, a psychiatrist will serve as a consultant to the patient's
primary care physician. This guideline reviews the treatment that
patients with HIV/AIDS may need. The psychiatrist should
either provide or advocate for the appropriate treatments.
This document is a practical guide to the management of patientsprimarily
adults over the age of 18with HIV/AIDS and represents
a synthesis of current scientific knowledge and rational clinical
practice. This guideline strives to be as free as possible of bias
toward any theoretical approach to treatment.
This practice guideline was developed under the auspices of
the Steering Committee on Practice Guidelines. The process is detailed
in the Appendix to this volume. Key features of the process include the
a comprehensive literature
review (description follows) and development of evidence tables;
initial drafting by a work group that included psychiatrists
with clinical and research expertise in HIV/AIDS;
the production of multiple drafts with widespread review,
in which 14 organizations and over 60 individuals submitted significant
approval by the APA Assembly and Board of Trustees;
planned revisions at regular intervals.
A computerized search of the relevant literature from MEDLINE,
PsycINFO, EMBASE, and AIDSLINE was conducted.
The first literature search was conducted by using MEDLINE
for the period from 1966 to June 1998 and used the key words "acquired
immunodeficiency syndrome,""HIV,""dementia,""mood disorders,""anxiety,""sleep,""depression
mania,""substance use," and "adjustment
The literature search conducted by using PsycINFO covered
the period from 1967 to March 1998 and used the key words "acquired
immune deficiency syndrome,""adjustment disorders,""human immunodeficiency
virus,""dementia," and "mood
The literature search conducted by using EMBASE covered the
period from 1980 to 1998 and used the key words "acquired
immune deficiency syndrome,""adjustment disorders,""human immunodeficiency
virus,""manic depressive psychosis,""depression," and "mood
The literature search conducted by using AIDSLINE covered
the period from 1980 to 1998 and used the key words "acquired
immunodeficiency syndrome,""HIV,""adjustment
disorders,""psychotherapy,""dementia,""treatment,""therapy,""therapeutic," and "mood
An additional literature search was conducted by using MEDLINE
for the period from 1990 to 1999 and used the key words "correctional
settings,""jail,""women,""minorities," and "suicide."
Additional, less formal, literature searches were conducted
by APA staff and individual members of the work group on HIV/AIDS.
The following executive summary is intended to provide an
overview of the organization and scope of recommendations in this
practice guideline. Because psychiatric treatment of patients with HIV/AIDS
requires the consideration of many factors, it cannot be adequately
reviewed in a brief summary. The reader is encouraged to consult
the relevant portions of the guideline when specific treatment recommendations
are sought. This summary is not intended to stand on its own.
Each recommendation is identified as falling into one of three
categories of endorsement, indicated by a bracketed Roman numeral
following the statement. The three categories represent varying
levels of clinical confidence regarding the recommendation:
[I] Recommended
with substantial clinical confidence.
[II] Recommended with moderate clinical
[III] May be recommended on the basis
of individual circumstances.
All psychiatrists need to have an adequate fund of knowledge
about HIV/AIDS. Because scientific knowledge regarding
virology, prevention, and interventions to treat HIV infection advances
rapidly, this guideline attempts to summarize current knowledge
and principles of treatment with the expectation that updated information
will be needed. For this reason, several pertinent web site addresses
have been included both in the text and in an appendix at the end
of the guideline. The reader is encouraged to use the web sites
to search for additional or more current information that will supplement
the information provided in this guideline. Section II provides
information about the following: the pathophysiology and virology
of HIV, the epidemiology of HIV/AIDS, transmission of HIV,
pathogenesis of HIV, assessment and staging of HIV disease, treatment
for HIV infection, impact of HIV on the central nervous
system, neuropsychiatric clinical syndromes, differential diagnosis of
neuropsychiatric syndromes, pediatric HIV/AIDS
syndromes, and prevalence of comorbid psychiatric conditions.
Section III serves as a guide for formulating and implementing
a treatment plan, and its outline is mirrored in Sections V and
VI, in which the data regarding prevention and treatment, respectively,
are provided. Readers may find it useful to first read Section III
and then refer to Sections V and VI for the scientific evidence
on which the treatment recommendations have been made.
Because there are many clinical and environmental features
that may influence treatment, Section IV provides additional information
on sociodemographic variables such as race/ethnicity, sexual
orientation, gender, age, economic factors, and setting (urban versus
rural). Specific clinical topics of suicidality, bereavement, axis
II disorders, and psychoneuroimmunology are also covered. Last,
information about special treatment situations such as alternative/complementary
treatments, institutional settings, and health care clinician issues is
Psychiatrists may encounter patients in the course of their
clinical work who are at risk for acquiring HIV infection. Optimum
management of patients at high risk for HIV infection uses a wide
range of psychiatric skills such as comprehensive diagnostic evaluations, assessment
of possible medical causes of new-onset symptoms, initiation of
specific treatment interventions, and a keen understanding of psychodynamic
issues [I]. Patients with substance
use disorders, patients with severe mental illness, and victims
of sexual abuse/crimes have specific risks for becoming
infected with HIV [I]. Psychiatric management
of individuals who, because of specific behaviors, are at risk for
HIV infection involves obtaining a risk history, considering the
need for HIV antibody testing, initiating risk reduction strategies,
and initiating postexposure prophylaxis with antiretroviral medication when
indicated. A psychiatrist will not be aware of a patient's
risk for HIV infection unless risk behavior is accurately assessed [I].
Psychiatrists should be knowledgeable about which specific risk
behaviors are more likely to result in HIV transmission [I].
Psychiatric units or individual practitioners who conduct HIV testing
should be aware of their obligation to provide the necessary pre-
and posttest counseling [I]. Because successful
risk reduction requires more than knowledge of risk, ongoing discussions
between patient and psychiatrist can help provide the motivating
and skill-building factors that help ensure consistent changes in
behavior [II].
Psychiatrists serve as primary clinicians of both medical
and psychiatric care in some institutional settings. Thus, administrators
of these facilities should formulate policies that support the full
range of HIV prevention steps outlined in this guideline [I].
Postexposure prophylaxis is recommended for known occupational exposure,
especially percutaneous or mucous membrane exposure, to blood or
other body fluids [I]. The American College of Obstetricians
and Gynecologists now recommends that an HIV antibody test be offered during
annual exams to all women seeking preconception care, not just pregnant
women [II].
Specific tasks that constitute the psychiatric management
of patients with HIV/AIDS include the following: establishing
and maintaining a therapeutic alliance; collaboration and coordination
of care with other mental health and medical providers; diagnosing
and treating all associated psychiatric disorders; facilitating
adherence to the overall treatment plan; providing education about
psychological, psychiatric, and neuropsychiatric disorders; providing
risk reduction strategies to further minimize the spread of HIV;
maximizing psychological and social/adaptive functioning;
considering the role of religion/spirituality; preparing
the patient for issues of disability, death, and dying; and advising
significant others/family regarding sources of care and
The development of a psychiatric treatment plan for patients
with HIV infection requires thoughtful and comprehensive consideration
of the biopsychosocial context of the illness [I].
When seeing a patient in consultation, it is important to gather
history about cognitive or motor symptoms and conduct a mental status
screening examination to determine whether neurocognitive deficits
are present [I]. Psychiatrists should be knowledgeable
about medication side effects and drug interactions of psychotropic
agents as well as HIV-related medications in order to provide optimum
patient care [I]. Psychiatric treatment of patients with
HIV infection should include active monitoring of substance abuse,
since it is often associated with risk behaviors that can lead to
further transmission of HIV [I]. Adherence is
of utmost concern with antiretroviral treatment because the regimens
are so unforgiving; even minor deviations from the prescribed regimen
can result in viral resistance and permanent loss of efficacy for
existing medications [I]. Psychiatrists can play
an important role in the promotion of patient adherence, since comorbid
psychiatric disorders (e.g., substance abuse or depression) have
been shown to adversely affect patient compliance with a complicated
treatment regimen [II].
Psychiatric disorders associated with HIV/AIDS should
be accurately identified and treated [I]. In adults
and children with HIV infection, changes in mental status or the emergence
of new psychiatric or cognitive disorders requires ruling out treatable
and reversible causes; medical causes are of increasing concern
if CD4 counts are low or viral load has begun to rise [I].
The more common diagnoses found in association with HIV/AIDS
are dementia and the spectrum of cognitive disorders; delirium;
mood disorders; substance use disorders; anxiety disorders; psychotic
disorders; adjustment disorders; sleep disorders; disorders
occurring in infants, children, and adolescents; and HIV-associated syndromes
with psychiatric implications. Both psychopharmacologic and psychotherapeutic
treatment strategies are often indicated.
Treatment of HIV-associated dementia consists of intervening
with combination antiretroviral therapy that targets the underlying
HIV infection, with consideration of whether the agents adequately
penetrate the central nervous system (CNS); management of symptoms associated
with HIV-associated dementia (e.g., agitation or fatigue) with antipsychotic
or stimulant agents, respectively, should be considered [I].
Delirium in the context of HIV infection may often be caused by
interactions between the many medications taken by HIV patients.
Management of delirium includes the judicious use of antipsychotic
medications, with many clinicians choosing atypical agents because
of their lower side effect profile; benzodiazepines are relatively
contraindicated [II].
The management of disturbances in mood, such as major depression
or mania, for patients with HIV infection is similar to that for
other patients with medical comorbidity [I]. Choice
of an antidepressant or mood-stabilizing agent may be influenced
by the antiretroviral regimen in place, and dose adjustments may
be necessary if drug-drug interactions are likely. A wide array
of antidepressant agents are effective in the treatment of HIV-associated major
depression, including newer agents such as the selective
serotonin reuptake inhibitors (SSRIs) [I] and
medications such as psychostimulants and testosterone [II].
Psychotherapy, particularly interpersonal psychotherapy, either
alone or in combination with antidepressant agents, is also an effective
treatment for HIV-related depression [II]. Mania
associated with HIV infection, particularly late in the course of
HIV disease, may be difficult to treat; however, treatment studies
suggest that traditional antimanic agents are effective and tolerated [II].
The constellation of other disorders associated with HIV infection
requires treatment. Substance use disorders are prevalent among
persons with or at risk for HIV infection, and treatment is a high priority [I].
Psychiatrists should be aware that by treating substance abuse,
they may well be preventing HIV infection. One component of a comprehensive
approach to HIV prevention among injection drug users is access
to sterile syringes [I]. Treatment of anxiety
and sleep disorders among HIV-infected patients has not been well
studied. For patients who are taking protease inhibitors, benzodiazepines
are generally contraindicated because of drug-drug interactions [II].
Thus, benzodiazepines should be given only as a short-term intervention
in most instances. Psychotic symptoms in late-stage HIV infection
are generally managed with atypical antipsychotic medications at
the lowest effective dose, since standard neuroleptic medications
have been associated with severe and difficult-to-treat extrapyramidal
side effects [I]. Adjustment disorders may require
treatment with psychotherapy or medication to prevent progression
to a more severe psychiatric disturbance [III]. HIV-associated
syndromes with psychiatric implications encompass wasting syndrome,
fatigue, pain, and sexual dysfunction. Wasting syndrome
has been effectively treated with testosterone (or its derivatives),
growth hormone, and thalidomide [I].
Psychostimulants are one of the main interventions used
for fatigue [II]. Chronic pain from peripheral
neuropathy is often treated with tricyclic antidepressants
and anticonvulsant medications, but published treatment studies
of pain syndromes in patients with HIV infection have not supported
their use [III]. In men, HIV-related hypogonadism
can be treated with testosterone replacement [II].
Treatment of children and adolescents with antiretroviral
medications has increased survival rates and slowed progression
to AIDS [I]. The effectiveness of treatment of
other mental and behavioral disorders associated with HIV infection
in children and adolescents is largely unstudied.
Identified in 1984, HIV is a human retrovirus (Figure 1).
A retrovirus contains RNA as its genetic material as well as the
enzyme reverse transcriptase required to translate RNA into DNA
within the human host cell. Once HIV RNA is transcribed into human
DNA through the process of replication, it becomes a functional
virus capable of producing profound immune deficiency, particularly
cell-mediated immune dysfunction (Figure 2).
As with other retroviruses, HIV has a rapid rate of genetic
mutation. HIV-1 is the form of the virus that causes disease in
most of the world, including the United States, Europe, Asia, Latin
America, and most of Africa. HIV-2, discovered in 1986, causes a
relatively small proportion of cases clustered in West Africa. Unless
specified, the term HIV used in this guideline will refer to HIV-1.
HIV selectively infects certain cells within the human body,
with the primary sites being blood mononuclear cells, particularly
T-helper (CD4) lymphocytes and lymphoid tissues.
HIV is neuropathic, invading the CNS early during the initial period
of infection.
Counter to earlier beliefs, HIV does not become "dormant" but
rather engages in an extraordinary battle with the immune system
that begins and continues after initial infection. Once a host is
infected with HIV, the virus begins a process of rapid replication,
with billions of viral particles made soon after infection (Figure
3). At the same time, the host immune system mounts a response.
The capacity of HIV to infect host cells and replicate, destroying
CD4 cells in the process, is counteracted by the capacity of the
host immune system to produce and maintain immune surveillance over
the replicating virus. Current knowledge suggests that there is
a viral "set point" that varies among individuals
and constitutes a balance between viral reproduction and the immune
response. This viral set point has prognostic significance (1).
The growth of knowledge about the virology and pathophysiology of HIV
has had enormous implications for treatment interventions.
HIV infection is a global pandemic, with cases of AIDS reported
in nearly every country in the world. According to the Joint United
Nations Programme on HIV/AIDS (UNAIDS), as of December 1999,
more than 33 million people in the world are estimated to be living
with HIV/AIDS, of which 95% live in the developing
world. Globally, more than 16 million people have died of AIDS since the
epidemic began (data available at http://www.unaids.org).
The Centers for Disease Control and Prevention (CDC) monitors
the incidence, prevalence, morbidity, and mortality from HIV/AIDS
in the United States (http://www.cdc.gov/nchstp/hiv_aids/dhap.htm).
Through December 1999, a cumulative total of more than 730,000 AIDS
cases have been reported to the CDC; there have been 430,441 total
deaths from AIDS in the United States (Table 1). Approximately 650,000–900,000
persons in the United States are currently infected with HIV, which is
about 0.3% of the population or 1 in 300 Americans.
Persons Living With
HIV Infection in 1999
Persons Living
With AIDS in 1999
Cumulative Deaths
as a Result of AIDS
Source. From
the CDC HIV/AIDS Surveillance Report (33).
In recent years, there has been a remarkable change in the
epidemiology of AIDS in the United States. The National Center for
Health Statistics has reported that age-adjusted death rates from
AIDS in the United States declined an unprecedented 47% from
1996 to 1997, and AIDS fell from 8th to 14th among leading causes
of death in the United States over the same time (2). For those
aged 25–44, AIDS dropped from the leading cause of death
in 1995 to the third-leading in 1996 and the fifth-leading in 1997
(2). The drop in deaths and AIDS incidence has been attributed to
the effectiveness of antiretroviral therapy, but the declines have
been less apparent among women and minorities.
At the same time, a study by the CDC found that despite the
decrease in AIDS deaths and incidence, the rate of
new HIV infections has remained the same: about 40,000 new cases
a year (3). Therefore, the overall prevalence of HIV infection in
the United States has increased (4). Prevention of HIV infection
remains a high priority.
Approximately 70% of new infections occur among men,
of which 60% are men who have sex with men, 25% are
injection drug users, and 15% are men exposed through heterosexual
contact (3). Among women, 75% of new infections occur through
heterosexual contact and 25% through injection drug use
(5). African American and Hispanic communities are two distinct
populations within which women, youth, and children are especially
HIV is transmitted through body fluids. It has been isolated
from a variety of body fluids, including blood, semen, vaginal secretions,
breast milk, urine, saliva, and tears. The risk of transmission through
contact with a given fluid is related both to the amount of virus
present in the fluid and to the type of exposure to it. HIV is found
in such small concentrations in tears, saliva, and urine that transmission
through casual contact with these fluids is theoretically possible
but highly unlikely. On the other hand, behaviors that lead to certain
types of exposure to blood, semen, vaginal secretions, and breast
milkall fluids with higher HIV concentrationsmay
lead to HIV transmission. HIV is spread primarily by unprotected
sexual intercourse, irrespective of gender or sexual orientation,
and sharing of unsterilized injection equipment for either medical
or illicit purposes. It can be transmitted from an infected mother
to an infant in utero during pregnancy, perinatally, or through
Sexual behaviors with exchange of body fluids can transmit
HIV. While the rate of HIV transmission is somewhat higher for the
recipient of semen than for the donating sexual partner, transmission
has been documented in both directions. Penile-anal and penile-vaginal
intercourse are considered the highest risk behaviors, with transmission
more likely in the presence of other sexually transmitted diseases
or genital lesions or during sexual activities that cause a rupture
of tissue or bleeding (Table 2).
Risk Level
Sexual Activity
No risk
Dry kissing
Body-to-body rubbing
Nipple stimulation
Using unshared inserted sexual devices
Being masturbated by partner without
semen or vaginal fluids
Erotic bathing and showering
Contact with feces or urine on intact
Theoretical risk
Wet kissing
Cunnilingus with barrier
Digital-anal and digital-vaginal intercourse,
with or without glove
Using shared but disinfected inserted
sexual devices
Low risk
Sharing nondisinfected personal hygiene
items (razors, toothbrushes)
Cunnilingus without barrier during
or outside menstruation
Fellatio and ejaculation, with or without
ingestion of semen
Fellatio, with or without condom
Penile-vaginal intercourse with condom
Penile-anal intercourse with condom
High risk
Penile-vaginal intercourse without
Penile-anal intercourse without condom
Coitus interruptus (intercourse with
withdrawal before ejaculation)
Source. From
Counselling Guidelines for HIV Testing (66).
Sharing the equipment used to prepare and inject drugs with
an HIV-infected person is a very efficient means of transmitting
HIV and essentially amounts to a direct inoculation of viral particles from
one person to another. The risk of transmission is directly related
to the concentration of virus present in the blood and the volume
of blood exchanged. Injection drug use is the second most common
risk factor for HIV infection, and injection drug users account
for an increasing proportion of AIDS cases (24% in 1997).
It has been estimated that there are more than 1.5 million injection drug
users in the United States (7).
Blood transfusion with infected blood products remains a significant
risk for acquiring HIV in some parts of the world. In the United
States, donated blood has been screened for antibodies to HIV-1
since 1985 and for antibodies to HIV-2 since 1992. Therefore, the
risk of transmission from a blood transfusion has become extraordinarily
lowless than 0.001%. To further ensure that donated
blood is not infected with HIV, since 1996 the American Red Cross
has used the HIV antigen test. This test helps address the problem
of false-negative HIV antibody tests in donors who may not have
produced detectable antibodies after their initial infection. Before
the use of lyophilized factor VIII, recurrent inoculation with pooled
donated factor VIII was a major source of HIV transmission in hemophilia patients.
Infection from mother to infant can occur during gestation,
delivery, or breast-feeding. Because breast milk contains significant
numbers of lymphocytes that can lead to HIV transmission from mothers
to newborns, it is recommended in the United States and other developed
countries that HIV-infected mothers bottle-feed and not nurse their
Cofactors can enhance but do not cause the transmission of
HIV. Physical cofactors include
the presence of sexually transmitted diseases (such as gonorrhea,
syphilis, and chlamydia, which may cause genital lesions) or genital/mucous
membrane bleeding during sexual activity. The use of mood or mind-altering substances
may serve as a behavioral cofactor
because they can lower sexual inhibitions, impair judgment, or increase
impulsivity. Data are inconclusive regarding the effect of mind-altering
substances on immunocompetence and HIV susceptibility or progression.
Three to 6 weeks after initial infection with HIV, there is
a burst of viral replication, with wide dissemination of the virus
throughout the body, particularly in lymphoid tissue and within
the CNS. During this acute phase, approximately 50%–90% of
people will experience a nonspecific "flu-like" syndrome
of varying severity with fever, sore throat, rash, lymphadenopathy,
and splenomegaly. Others do not have this seroconversion syndrome
and may be unaware of their infection (8). As the host's
immune system begins to recognize the pathogen and mounts a response
to control the infection, plasma viral titers may drop 100-fold
within 1 or 2 months of initial infection. When the host produces
circulating antibodies against HIV, the host is said to "seroconvert," demonstrating
a positive HIV antibody test. Although the immune system may appear
to control the initial infection, chronic viral replication persists.
There have been recent discoveries that "resting CD4 T
cells" become infected rapidly after HIV transmission,
and once HIV hides within resting T cells, antiretroviral therapy
is unlikely to affect this sanctuary for HIV (9, 10).
The acute phase is followed by a clinically asymptomatic phase,
during which the body has established a dynamic balance between
the capacity of the virus to replicate and infect new CD4 cells and
the capacity of the body to produce more CD4 cells. Even so, as
many as 10 billion viral particles are produced daily, with a plasma
virus half-life of about 6 hours. The asymptomatic phase may last for
many years until symptoms arise that indicate that HIV infection
is progressing. Progression to a symptomatic phase of illness may
occur more rapidly in those with immune systems that are compromised
before HIV infection and in infants with undeveloped immune systems.
Other factors influencing disease progression include mutations
of cell surface receptors and host factors such as HIV-specific
cytotoxic lymphocyte response (Figure 3).
Viral load, a measurement of how many viral particles are
present in a cubic millimeter of blood, is determined
by several different assays that can detect as few as 20 viral particles
per cubic millimeter of blood. Below that threshold, viral load
is reported as "nondetectable." This does not mean
that there is no HIV in the blood. Furthermore, this method does
not measure the amount of HIV in lymphoid tissue, semen, or CNS.
While some studies have shown a small correlation between serum
viral load and lymphoid tissue and CSF viral load, in later stages
of HIV infection, plasma and CSF viral load are largely uncorrelated
(11, 12). Thus, the CNS can be seen as an independent "reservoir" of
HIV replication. Current practice is to use serum viral load measurements,
in combination with assays of immune cells such as CD4 counts and
genotypic testing for viral resistance, to guide clinical decisions
about the initiation of or changes in antiretroviral medication (13–15).
New knowledge about the life cycle of HIV and the discovery
of several classes of medications that disrupt the virus at different
points in the replication cycle (Figure 4) benefit many patients
who receive multidrug regimens, known as potent, combination, or
highly active antiretroviral treatment. However, these regimenswhich
involve at least three medications, with short- and potential long-term
side effects, taken multiple times per day for the life of the infected
personrequire strict adherence. The behavioral and psychological
burden of early intervention is thus a mitigating factor against
such an early and aggressive treatment approach. The rapid pace
of changes to potent, combination, or highly active antiretroviral
treatment guidelines adds to uncertainty about such interventions.
Medications that can be taken less frequently are being developed
to make the regimens more manageable.
HIV infection usually leads to clinical diseases that affect
almost every organ system and present with a wide range of symptoms
and syndromes. Accurate assessment and diagnosis of systemic as well
as CNS impairment requires close medical and psychiatric management,
with increasing vigilance as immune competence declines and the
possibility of life-threatening disorders increases.
The CDC Revised Classification system for HIV infection and
AIDS used CD4 counts and staging of illness (Table 3) to establish
clinical categories for HIV disease. Generally, AIDS is defined
by certain conditions marking advanced immunosuppression, such as
a diagnosis of opportunistic infections (e.g., Pneumocystis
carinii pneumonia) or other conditions (e.g., dementia
or wasting). AIDS-defining criteria are listed in Table 4.
T Cell Count
Acute (primary) HIV or persistent
generalized lymphadenopathy;
patient is asymptomatic
Patient is symptomatic,
but condition does not meet criteria for category A or C
Patient has an AIDS
indicator conditiona
Source. From the
Centers for Disease Control and Prevention (1717).
aAs of Jan. 1, 1993, persons with
AIDS indicator conditions (categories C1–C3) as well as
those with T lymphocyte counts less than 200/μl (category
A3 or B3) were categorized as AIDS cases in the United States and
its territories.
CD4 Cell Count (cells/mm3)
Kaposi's sarcoma
Tuberculosis reactivation
Herpes zoster
Herpes simplex
Bacterial sinusitis/pneumonia
Pneumocystis carinii pneumonia
Systemic fungal infections
Primary tuberculosis
Cerebral toxoplasmosis
Progressive multifocal
Peripheral neuropathy
Cervical carcinoma
Cytomegalovirus disease
Disseminated Mycobacterium avium-intracellulare complex
Non-Hodgkin's lymphoma
Central nervous system lymphoma
HIV-associated dementia
Most of the world's HIV-infected population has little
if any access to antimicrobial therapies for consequences of immune
deficiency, let alone combination antiretroviral treatment. In the
United States, revised standards of care for the treatment of HIV
infection have improved treatment effectiveness, increased survival
for patients, and potentially lessened development of viral resistance.
Treatment is accomplished through numerous combinations
of antiretroviral agents from four classes: nucleoside analogue
reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors,
protease inhibitors, and the newest class, nucleotide analogues
(Table 5). Guidelines for the use of antiretroviral agents in HIV-infected
adults and adolescents are available from the HIV/AIDS
Treatment Information Service (http://www.hivatis.org).
Drug Name
Nucleoside analogue reverse
transcriptase inhibitors
Lamivudine-zidovudine (combination)
Nonnucleoside reverse
transcriptase inhibitors
Protease inhibitors
Lopinavir-ritonavir (combination)
Nucleotide analogues
called dideoxyinosine (ddI).
bFormerly called 3TC.
cFormerly called d4T.
dFormerly called 2'3'-dideoxycytidine
eFormerly called azidothymidine
The current goal of antiretroviral therapy is to reduce viral
load to undetectable levels and maintain such remission without
interruption. Evidence suggests that the therapies suppress replication
but do not eradicate HIV from all parts of the body, particularly
lymphoid tissue and the brain. Not all patients who initiate antiretroviral
therapy respond. The lack of clinical response is likely explained by
problems with adherence, suboptimal antiretroviral treatment potency,
and genetic mutation of HIV strains (18). Many patients experience
substantial side effects, and it is not uncommon for changes to
be made in antiretroviral drug regimens because of such side effects.
Adverse effects include lipodystrophy (fat redistribution syndromes),
hyperlipidemia, nephrotoxicity, bone marrow suppression, neuropathy,
and elevation of glucose to possibly diabetes mellitus–causing
levels (19). Patients often experience nausea, diarrhea, sleep disturbances,
and rashes. The cost of antiretroviral drugs alone is about $12,000
per year for a single individual, and the long-term health consequences of
these agents are not known.
Adherence is of utmost concern with antiretroviral treatment
because the regimens are so unforgiving; even minor deviations from
the prescribed regimen can result in viral resistance and permanent
loss of efficacy for existing medications. Studies of antiretroviral
treatment continue to indicate that near-perfect adherence is needed
to adequately repress viral replication. The potential implications
of nonadherence are troubling, as evidenced by a study
that found a primary viral resistance rate to antiretrovirals of
16.3% among a cohort of recently infected individuals (20).
This study documented what was earlier considered a theoretical
concernnamely that persons newly infected with HIV may
carry viral strains already resistant to available antiretroviral
agents, indicating transmission of resistant viral strains from
persons who were taking nonsuppressive multiple drug therapy or
who were nonadherent to treatment (21).
As the U.S. HIV epidemic spreads increasingly among disadvantaged
persons with limited resources who may have multiple comorbid disorders,
significantly more psychosocial stressors, and less access to ongoing
primary or mental health care, these individuals are at risk of
not receiving the recommended treatment for HIV infection. Services
for HIV patients must balance medical interventions with the emotional,
economic, and social supports required for good quality of life
and prevention of further transmission.
Clinical evidence for direct infection of the CNS by HIV emerged
in the mid-1980s, when patients began to survive their presenting
opportunistic infections but went on to develop neuropsychiatric syndromes
that could not be attributed to CNS opportunistic infections or
neoplasms. Additional evidence included signs of neurocognitive
impairment in adults, loss or arrest of developmental milestones
in children, ability to culture HIV from CSF, neuropathological
lesions of the brain at autopsy, and abnormalities observed through
brain imaging techniques, including cerebral atrophy.
HIV invades the CNS early in the course of infection, entering
by way of macrophages, which along with microglial cells
are largely responsible for HIV replication within the CNS. While
HIV does not infect neurons in the CNS, it causes neuronal death
by other mechanisms. It is hypothesized that HIV infection of microglial
cells in the CNS causes the elaboration of neurotoxins that, in
turn, cause neuronal damage (22, 23). Neuronal dysfunction usually
takes place at a slow rate, and it is not clear whether the immune
system plays a role in keeping HIV in the CNS under control (24). Some
researchers believe that high systemic viral load may "drive" neurological
disease (25), but there is converging evidence that the CNS compartment
differs from that of the peripheral bloodstream, with independent
viral evolution/mutation (leading to viral resistance)
and different viral load decay kinetics (26, 27).
Major unanswered questions remain about the natural history
of HIV in the CNS and whether current antiretroviral treatment regimens
penetrate the blood-brain barrier sufficiently to reduce viral replication
to the levels seen in the systemic circulation. Neuroprotective
agents, immune modulators that increase macrophage activity within
the CNS, and vaccines that boost immune response rather than prevent
infection are all potential additional strategies to address neuropsychiatric
HIV infection can lead to neuropsychiatric syndromes that
can occur at various stages of infection. Clinicians need to be
aware of this possibility when evaluating new patients and observing
changes in the patients whom they treat (28). Symptomatic HIV infection
of the brain generally affects cognitive and motor functioning.
Subtle neuropsychological impairment may be found in 22%–30% of
otherwise asymptomatic patients with HIV infection (29, 30); these
findings may or may not have functional significance. There is ample
evidence for HIV causing the disorders HIV-associated dementia and
HIV-associated minor cognitive motor disorder. HIV can affect other
areas of the nervous system, causing syndromes such as painful sensory
peripheral neuropathy or vacuolar myelopathy of the dorsolateral
columns of the spinal cord. There are limited data in support of
HIV infection of the CNS resulting in syndromes such as psychosis
(31) or mania (32–34).
What separates HIV-associated dementia and HIV-associated
minor cognitive motor disorder from the less severe cognitive changes
seen in some HIV patients are the significance and duration of the functional
deficits (Table 6, Table 7). HIV-associated minor cognitive motor
disorder is a less severe disorder than HIV-associated dementia
but does not necessarily progress to HIV-associated dementia (36).
HIV-associated minor cognitive motor disorder is important to diagnose
and treat, since it is thought to involve neuronal cell dysfunction
rather than actual cell death, as seen in HIV-associated dementia.
Both HIV-associated minor cognitive motor disorder and HIV-associated
dementia are independent risk factors that decrease survival among
patients with HIV infection (37, 38).
1. Acquired abnormality in at least two of the following
cognitive abilities (present for 1
Cognitive decline verified by history
and mental status examination. When possible, history should be
obtained from an informant and examination should be supplemented
by neuropsychological testing. The cognitive dysfunction must cause
impairment of work or in activities of daily living, with impairment
not attributable solely to severe systemic illness.
Speed of processing
Visuospatial skills
Memory learning
2. At least one of the following:
Acquired abnormality in motor function or performance
Abnormality verified by physical examination, neuropsychological
tests, or both.
Decline in motivation or emotional control or change
in social behavior
Change characterized by any of the
following: apathy, inertia, irritability, emotional lability, or
new-onset impaired judgment characterized by socially inappropriate
behavior or disinhibition.
3. Absence of clouding of consciousness during a period
long enough to establish the presence of criterion 1
4. Exclusion of another etiology
by history, physical, and psychiatric examination and appropriate
laboratory and radiologic tests
Alternate possible etiologies include
active central nervous system opportunistic infections or malignancy,
psychiatric disorders (e.g., depressive disorders), active substance
abuse, or acute or chronic substance withdrawal.
Source. From the
American Academy of Neurology (3535).
Probable Diagnosis (must meet all four
1. Acquired cognitive/motor/behavioral
abnormalities, verified by both a
reliable history and by neuropsychological tests
2. Mild impairment of work or activities of daily living
3. Does not meet criteria for HIV dementia or HIV myelopathy
4. No other etiology present
Source. From the American Academy of Neurology
aA possible diagnosis of minor cognitive motor disorder can
be given if criteria 1–3 are present and either 1) an alternative etiology
is present and the cause of number 1 is not certain, or 2) the etiology
of criterion 1 cannot be determined because of an incomplete evaluation.
In contrast to Alzheimer's disease, which is a cortical
dementia, HIV-associated dementia is classified as a subcortical
dementia. HIV-associated dementia can produce different combinations
of a clinical triad of progressive cognitive decline, motor dysfunction,
and behavioral abnormalities. Symptoms commonly found in HIV-associated
dementia include psychomotor slowing, decreased speed of information
processing, impaired verbal memory and learning efficiency, and,
later on, impairment in executive functioning. Behavioral manifestations
vary throughout the range of HIV-related neurocognitive
disorders, ranging from apathy to psychosis.
While the prevalence rate for HIV-associated dementia was
estimated in the past to be 15%–20% of
all AIDS patients (39), the incidence rate for HIV-associated dementia
may be affected by the use of potent combination therapies. One
report from the Multicenter AIDS Cohort Study (40) demonstrated
declines of at least 50% in the incidence of HIV-associated
dementia and CNS opportunistic complications (e.g., toxoplasmosis
and primary CNS lymphoma) since the introduction of combination
antiretroviral treatment in 1996. A second report has estimated
that the incidence of HIV-associated dementia decreased from 21.1/1000
person-years in 1990–1992 to 14.7/1000 person-years in
1996–1997 (40). On the other hand, one group found that
for patients who received combination antiretroviral treatment,
the proportion of HIV-associated dementia as a percentage of all
AIDS-defining illnesses rose from 4.4% to 6.5% between
1995 and 1997 (41). This shift in the rate of HIV-associated dementia
is thought to reflect the decrease in rates of other AIDS-defining
conditions, thereby leading to the relative rise in HIV-associated
dementia cases.
Because HIV affects subcortical areas of the brain, it has
been postulated that HIV may cause syndromes relating to mood and
psychosis. New-onset psychosis and mania in HIV-infected
patients tend to present at later stages of HIV disease and often
occur in association with cognitive motor impairment. Lyketsos and
colleagues (34) have described HIV-infected patients with so-called
AIDS mania who present at advanced stages of HIV infection but generally
have no family or personal history of mood disorder and have higher
rates of comorbid dementia. They hypothesized that mania in this
context is directly caused by HIV brain infection. Mijch and colleagues
(32) conducted a prospective case-control study to test the hypothesis
put forward by Lyketsos et al. In their study of 19 HIV patients
with secondary mania, they found that treatment with zidovudine,
which is known to penetrate the blood-brain barrier well, provided
a protective effect against the development of mania. In addition,
they found the incidence rate of HIV-associated dementia in the
subjects with mania to be significantly greater than in HIV subjects
without mania.
New-onset psychotic symptoms have been reported in HIV-positive
individuals in the absence of medical/iatrogenic
causes or concurrent substance abuse (42, 43). One case-control
study systematically examined patients with HIV infection that predated
the onset of psychosis (31). In this study, the psychotic subjects
had significantly higher rates of past stimulant and sedative-hypnotic
abuse and higher mortality at follow-up. While the study was limited
by a sample size of 20, the authors postulated that direct effects
of HIV infection on the brain could be one possible cause of new-onset psychosis
in their subjects.
Differential diagnosis of an acute change in mental status
includes but is not limited to delirium. Delirium occurs frequently
in the medically ill and is more likely when a patient's
illness is more severe. Estimates of rates of delirium in HIV patients
range from 43% to greater than 65% in late-stage
AIDS (44–46). Definition and management of the syndrome
of delirium is well described in the APA Practice
Guideline for the Treatment of Patients With Delirium (47;
included in this volume). Identification of the delirious state
and intervention to correct underlying causes reduces morbidity
and mortality. In persons with HIV infection, the most common causes
are iatrogenic and psychoactive-substance-induced toxicity, infection,
neoplasms, and metabolic disturbances. Some antiretroviral
medications can cause delirium (e.g., zidovudine at high doses [48] or
efavirenz [49]) (Table 8).
Medications and other drugs (not exhaustive)
Amphotericin B
Cryptococcal meningitis
Encephalitis due to HIV, herpes, cytomegalovirus
Progressive multifocal leukoencephalopathy
Mass lesions
Opiate analgesics
Zidovudine or didanosine
Drug or alcohol withdrawal
Endocrine dysfunction/metabolic abnormality
Hypoglycemia due to pentamidine, protease inhibitors
Hypoxia due to pneumonia
Nonendocrine organ dysfunction
Renal failure due to HIV nephropathy
or medication toxicity
Liver failure due to comorbid hepatitis
and medication toxicity
Nutritional deficiencies
Wasting syndrome
Failure to replace trace elements or vitamins in total
parenteral nutrition
Source. Adapted
from Bialer et al. (5050).
The term "HIV encephalopathy" is occasionally
used to refer to acute-onset cognitive deficits in adults, but its
definition and usage vary. A wide range of conditions that primarily
involve the CNS needs to be considered within the psychiatric differential
diagnosis, since these conditions may present with psychiatric symptoms
or cause psychiatric syndromes including psychosis (with or without
an affective component) and mood episodes (mania, hypomania, depression)
(51) (Table 9). The same concerns exist for medications commonly
used to treat conditions associated with HIV infection (Table 10).
Type of Manifestation
Acute HIV-1 infection
Viral meningitis
Ascending polyneuropathy
Opportunistic infections (late HIV-1 infection)
Toxoplasma cerebritis
Progressive multifocal
tuberculosis meningitis
Cytomegalovirus encephalitis
Herpes simplex encephalitis
Neoplastic disease (late HIV-1 infection)
CNS lymphoma
Other manifestations
HIV-associated minor cognitive motor disorder
Target Illness
Side Effects
Herpes encephalitis
Visual hallucinations, depersonalization,
tearfulness, confusion, hyperesthesia, hyperacusis, thought insertion, insomnia
Delirium, peripheral neuropathy, diplopia
-Lactam antibiotics
Confusion, paranoia, hallucinations,
mania, coma
Depression, loss of appetite, insomnia,
Psychosis, somnolence, depression,
confusion, tremor, vertigo, paresis, seizure, dysarthria
Nervousness, anxiety, confusion, seizures,
insomnia, peripheral neuropathy
Nightmares, depression, confusion
Paresthesias, seizures, headache, irritability,
hallucinations, confusion
Depression, weakness, headache, myalgias,
Depression, agitation, hallucinations,
paranoia, impaired memory, anxiety
Insomnia, mania
Encephalopathy (at high dose)
Confusion, anxiety, lability, hallucinations
Mania, loss of appetite, insomnia,
nightmares, confusion, malaise
Psychosis, delirium, seizures, anxiety,
insomnia, depression
Headache, asthenia, malaise, confusion,
depression, seizures, excitability, anxiety, mania, early morning awakening,
Psychosis, delirium, confusion, depression,
Hallucinations, olfactory disturbance
Depression, loss of appetite, headache
Hallucinations, headache, ataxia, sensory
Headaches, confusion, impaired concentration,
somnolence, asthenia, depression, seizures, peripheral neuropathy
Headache, malaise, asthenia, insomnia,
unusually vivid dreams, restlessness, severe agitation, mania, auditory hallucinations,
Source. Adapted
from Grant and Atkinson (5252).
In adults and children with HIV infection, changes in mental
status or the emergence of new psychiatric or cognitive disorders
requires ruling out treatable and reversible causes; medical causes are
of increasing concern if CD4 counts are low or viral load has begun
to rise. Psychiatrists should consider adding assessments of basic
immune function and viral load, CSF examination, and brain imaging
studies to the standard medical workup of new- or acute-onset psychiatric
syndromes for patients with or at high risk for HIV infection (Table 11).
Physical/neurologic examination
Focal deficits may indicate
space-occupying lesion (e.g., CNS lymphoma, toxoplasmosis, progressive
multifocal leukoencephalopathy)
Sensory changes, which may
indicate peripheral neuropathy
Ataxia or changes in gait, which may indicate
Laboratory analyses
CBC with differential
Serum chemistries
Arterial blood gas in patients with pneumonia
VDRL, fluorescent treponemal antibody
B12, folate
MRI, to rule out space-occupying lesion (progressive
multifocal leukoencephalopathy)
Lumbar puncture, to rule out acute infection (e.g.,
cryptococcal meningitis, herpes, toxoplasmosis, syphilis)
Neuropsychological testing
AIDS Dementia Rating Scale
Finger Tapping Test
Trail Making Test
Source. Adapted from Bialer et al. (5050).
To date, the proportion of children born with HIV who survive
until the age of 9 is approximately 50%, but antiretroviral
interventions will increase the number of infected youth who enter
adolescence. HIV-related symptoms may develop at any age, but a
prospective collaborative study found that only 10% of
children were symptomatic before the onset of an AIDS-defining illness
Certain clinical presentations characterized by lymphadenopathy,
parotitis, skin diseases, and recurrent respiratory tract infections
are associated with longer survival, while lymphoid interstitial pneumonitis
and thrombocytopenia form an intermediate survival group.
The worst prognosis is associated with bacterial infections, progressive
neurological disease, anemia, and fevers (54).
HIV infection that occurs at the time of birth rather than
early in gestation is thought to be associated with a better prognosis.
While at any given time many HIV-infected children may not experience
significant HIV-related medical morbidity, their overall health
outcome may be compromised by the conditions of poverty.
The impact of HIV on the developing nervous system of children
is more significant than on the developed adult nervous system,
and certain cognitive deficits may occur in some infected youth. The
term "dementia" is not commonly used to describe
cognitive deficits in children by pediatricians or child psychiatrists,
who refer to this condition as either HIV-associated progressive
encephalopathy or HIV encephalopathy. Nonetheless, "dementia
due to HIV disease" in children is specifically mentioned
in DSM-IV (p. 148).
HIV-associated progressive encephalopathy in children is characterized
by a triad of symptoms: impaired brain growth, progressive motor
dysfunction, and loss or plateau of developmental milestones (55).
Progressive encephalopathy needs to be distinguished from mental
retardation secondary to other causes, such as maternal drug addiction
and prematurity, which can be determined only by longitudinal assessment.
Despite the general fact that progressive encephalopathy is observed
in the context of immunosuppression, markers of immunologic functioning
(e.g., CD4 count) do not correlate with degree of neurocognitive
impairment (54). The prevalence rate of progressive encephalopathy
in a cohort of 128 HIV-infected children was 21% during
a mean follow-up period of 24 months. Progressive encephalopathy
was the first AIDS-defining condition in 67% of the group, and
mean survival after diagnosis was 14 months (56).
Although many children with HIV are considered to be asymptomatic,
numerous studies document at least some cognitive and language delays
(57). In a sample of 36 HIV-infected children who were less than
10 years old, brain abnormalities detected by means of computerized
tomography scans were significantly correlated with receptive and
expressive language deficits, with expressive language more severely
impaired than receptive language among those children with progressive encephalopathy
(58). In addition, visual motor deficits are common and may be correlated
with disease progression (59).
Since early in the HIV epidemic, researchers have studied
the prevalence of psychiatric disorders in persons with HIV infection
(60–63). Often these psychiatric disorders predated HIV
infection or occurred during the course of living with the disease;
they are not necessarily attributable to neuropathic effects of
HIV. Psychiatric illness is generally related to poorer functioning
and quality of life as well as increased use of HIV-related hospital
services (64). A study conducted by researchers in California found
that depression was associated with shorter survival times in men
with HIV infection (65).
Prevalence rates of psychiatric disorders reported in published
studies vary widely. In general, higher rates of psychiatric disorders
are seen in later stages of HIV infection and are reported in studies
that assess patients receiving care in HIV medical or psychiatric
clinics rather than community-based samples (66). On one extreme,
recent data from the national, multisite HIV/AIDS Mental Health
Services Demonstration Program revealed high rates of depression
(60%), dysthymic disorder (25%), and anxiety disorders
(25%) among persons seeking HIV-related mental health services
in the public sector (67). The study found high rates of comorbid
substance use disorders, with nearly 50% of all patients
also having a diagnosis of alcohol or drug dependence. These higher
rates are most likely linked to characteristics of the population
studied: HIV-positive individuals voluntarily seeking psychiatric
care, a population that may be more reflective of patients receiving
care from community mental health clinics. In contrast, prevalence
studies in selected community-based samples have found much lower
rates of psychiatric disorders, such as rates of major depressive disorder
in the 4%–14% range (68–73).
HIV prevention strategies are an essential component of the
comprehensive treatment of specific psychiatric populations and
for other psychiatric patients who manifest high-risk sexual and
drug use behavior. Some psychiatric patients, such as those confined
to forensic units, in long-term hospitals, and locked nursing homes
have almost no access to preventive strategies other than those
provided and supported by staff. Administrators and institutions
should formulate policies that support the full range of HIV prevention
steps outlined in this section. Primary prevention strategies are
those that seek to avert initial infection. Secondary and tertiary
prevention strategies target infected individuals in order to prevent
further transmission and reduce HIV-related medical complications,
Optimum management of patients at high risk for HIV infection
involves a wide range of psychiatric skills: comprehensive diagnostic
evaluations, assessment of possible medical causes of new-onset
symptoms, initiation of specific treatment interventions, and a
keen understanding of psychodynamic issues. In some institutional
settings, psychiatrists serve as primary clinicians of both medical
and psychiatric care. In such situations, psychiatrists should be
mindful to include HIV risk assessment and prevention as part of
patients' treatment plans.
A psychiatrist will not be aware of a patient's risk
for HIV infection unless risk behavior is accurately assessed. Such
an assessment should be considered in every psychiatric evaluation
in order to identify individuals who are at high risk due to specific behaviors.
Factors such as acute episodes of psychiatric illness,
stressful or traumatic life events, and the developmental stage
of the patient (e.g., initiation of sexual activity in adolescents)
contribute to the need for ongoing appraisal of patient risk. Psychiatrists
are particularly well-placed to assess HIV risk because they often
follow patients for lengthy periods of time, which allows for multiple
opportunities to assess behavior (74).
At times, the clinical state of the patient may preclude an
accurate assessment, such as when the patient is acutely psychotic
or intoxicated. In this situation, the risk history may need to
be obtained either when the patient is able to provide valid answers
or with the assistance of family or friends. Psychiatrists should
be knowledgeable about which specific sexual behaviors are more
likely to result in HIV transmission (Table 2). When conducting
an assessment of risk behavior, psychiatrists should convey a nonjudgmental
When carrying out a risk assessment, it is important to clarify
the vocabulary and cultural beliefs of the patient. For instance,
it is not uncommon for patients and clinicians to use different
terms to describe sexual or drug use behaviors, and slang terms
change quickly. The National Institute on Drug Abuse has published
a community drug alert that outlines common street drugs and their
slang names, which is available at http://www.drugabuse.gov. Clinicians
may be able to clarify risk behavior terms by first describing a
risk behavior and then asking a patient what he or she would call
that behavior (Table 12).
Frequency of sexual intercourse (vaginal, anal, oral)
Number, gender, and known HIV risk of sex partners
Whether the patient has traded sex (for money, drugs,
a place to stay, cigarettes)
Past and current symptoms of sexually transmitted infections
Use of condoms and other contraceptive methods
Use of drugs, particularly those that are injected
or sniffed
Sharing of needles, syringes, or other injection equipment
Source. From McKinnon et al. (7474).
Attitudes about HIV antibody testing have changed with the
development of HIV treatment interventions and educational efforts.
Formerly, patients were unwilling to learn their HIV status, since
knowing could cause emotional distress, could engender possible
discrimination, and did not lead to better clinical outcomes. Public
policy now promotes earlier identification of HIV infection so that
newly infected persons can be medically monitored and receive antiretroviral
treatment as appropriate. Yet HIV testing still carries risks due
to worries and fears associated with HIV/AIDS, as well
as the possibility of physical assault by a partner or other relation
after HIV diagnosis (75). Disclosure of HIV status to family, friends,
or employers can be quite problematic for some patients.
Discussion of the pros and cons of a routine baseline HIV
test are part of a comprehensive approach to HIV prevention in high-risk
patients. Psychiatric units or individual practitioners who conduct HIV
testing should be aware of their obligation to provide the necessary
pre- and posttest counseling (76). Elements of pre- and posttest
counseling include an explanation of the HIV test, including risks and
benefits, confidentiality of the results, discussion of
risk behavior and risk reduction strategies, and plans for dealing
with a positive or negative test result. Federal guidelines for
counseling have been established by the CDC (http://www.cdc.gov/hiv/pubs/hivctsrg.pdf).
Clinicians should remember that the timing of when to undergo
HIV testing is a distinct clinical decision. For instance, it is
generally not advisable to test a patient for HIV while he or she
is confused or intoxicated with alcohol or drugs. In the event that
a patient cannot give informed consent, the psychiatrist should
be familiar with the local legal requirements regarding HIV testing
and disclosure (77). Anonymous and confidential HIV testing is often
provided by state public health agencies or community-based organizations;
some patients prefer anonymity and may be more likely to agree to testing
given this option. Many state health departments conduct "partner
notification" or prevention counseling and referral services
to identify and test past or present sexual partners or drug injection equipment-sharing
partners of a newly reported HIV-seropositive person.
The American College of Obstetricians and Gynecologists now
recommends that an HIV antibody test be offered during annual exams
to all women seeking preconception care (not just pregnant women),
which reflects the growing awareness that many women may not properly
assess their personal risk for HIV infection (78). This recommendation
goes beyond the previous recommendation that pregnant women undergo
HIV antibody testing so that HIV-infected women can consider treatment
with antiretroviral medication. For female patients who are at risk
for HIV infection and for pregnancy,
conducting a baseline pregnancy test along with a baseline HIV test
is advised.
Risk reduction strategies include education of patients about
behaviors that place them at risk for HIV infection, active discussions
of changes in behavior, and treatment of problems that promote risky
behavior. It is important to view undergoing an HIV antibody test
as a "teachable moment," when counseling about
risk for HIV can be tailored to the specific behavior of the patient
and an individualized risk reduction plan can be developed.
Because successful risk reduction requires more than knowledge
of risk, ongoing discussions between patient and psychiatrist can
help provide the motivating and skill-building factors that help ensure
consistent changes in behavior. Psychiatrists should consider unconscious
motivations that may contribute to risk-taking behavior when developing
risk reduction strategies. Some patients may need to be referred
to community-based organizations or other clinicians who offer specific
risk reduction programs (e.g., needle exchange programs or skills
training groups). For some patients, risk reduction strategies can
include extended counseling and case management, such as that modeled by
the CDC (79).
When appropriate, psychiatrists should determine whether patients
have access to condoms and the skills to use them (Table 13). Skills
to discuss and negotiate safer sex with partners may need to be
developed; psychotherapy can provide an opportunity to practice
communication skills through role playing. Clinicians should be
alert to feelings of powerlessness in sexual situations for patients with
histories of sexual abuse and to the real possibility of violence
for some if a sexual partner is threatened or angered.
Condoms must be used consistently and correctly to
provide maximum protection. Consistent use means using a new condom
with each act of intercourse. Latex condoms and polyurethane condoms provide
protection; lambskin condoms should not be used. Correct condom
use includes all of the following steps.
Check the expiration date.
Use a new condom for each act of vaginal,
anal, or oral intercourse.
Put on the condom as soon as erection
occurs and before any vaginal, anal, or oral contact with the penis.
Apply lubricant to penis before and
after putting the condom on. This will provide greater satisfaction for
both the insertive and the receptive partners.
Hold the tip of the condom and unroll
it onto the erect penis, leaving space at the tip of the condom, yet
ensuring that no air is trapped in the tip of the condom.
Adequate lubrication is important to prevent condom
breakage, but use only water-based lubricants, such as glycerine
or lubricating jellies (which can be purchased at any pharmacy).
Oil-based lubricants, such as petroleum jelly, cold cream, hand
lotion, or baby oil, can weaken the condom.
Withdraw from the partner immediately
after ejaculation, holding the condom firmly to the base of the
penis to keep it from slipping off.
Source. From the CDC National Center for HIV,
STD and TB Prevention, Division of HIV/AIDS Prevention (8080).
Psychiatric conditions that could theoretically increase patient
risk for engaging in high-risk behavior include impulse control
disorders, untreated depression, hypersexuality associated with mania,
psychotic disorders, mental disorders due to a general medical condition,
binge alcohol or drug use, and personality disorders.
The premise underlying postexposure prophylaxis is that chemoprophylaxis
during a window of opportunity may prevent initial cellular infection
and local propagation of HIV, thus allowing the host immune defenses
to eliminate the inoculum of virus (81). Currently, postexposure
prophylaxis is recommended for known occupational exposure, especially
percutaneous or mucous membrane exposure, to blood or other body
Psychiatrists who serve as administrators of mental health
facilities should formulate policies and protocols for the expedient
treatment of health care professionals or patients who have had
such exposure. The protocol requires a rapid assessment of risk
and, where risk is present, beginning a multiple drug regimen as
soon as 1–2 hours after exposure and not later than 24–36
hours. It further requires 4 weeks of treatment with two or three
antiretroviral agents that can have significant side effects.
The CDC has issued guidelines for the use of antiretroviral
medication following health care worker occupational exposure to
HIV (82). There is a National Clinicians' Postexposure
Hotline (888-448-4911) that can be accessed 24 hours a day for guidance
in cases of possible or known exposure to HIV. A web site (http://www.ucsf.edu/hivcntr)
offers a wealth of information to address this issue.
Data are being gathered to evaluate the use of postexposure
prophylaxis in other exposure situations, but it is being increasingly
offered for known or possible sexual exposure to HIV. Public health
messages should emphasize that postexposure prophylaxis should be
used only when primary prevention methods such as use of condoms
or avoidance of high-risk behaviors have failed. Clinicians should
counsel patients who receive postexposure prophylaxis to reduce
their chance of future exposure (81).
The best way to prevent the spread of HIV through injection
drug use is effective primary prevention of drug use. For people
who are already injecting opioids, eliminating this behavior through
adequately dosed substitution therapy, such as methadone or a long-acting
form of methadone, l--acetylmethadol
(LAAM), can serve an HIV prevention function.
Harm reduction policies have received more support in the
last decade due to the spread of AIDS among injection drug users.
The primary purpose of harm reduction is to decrease the negative consequences
of drug use (83). As opposed to a policy of abstinence, harm reduction
approaches realistically assume that some individuals will continue
to use drugs. In this framework, a hierarchy of goals is established,
with more immediate or attainable ones achieved on the way to risk-free
use or possible abstinence. Risk reduction strategies such as methadone
maintenance treatment, needle education and bleach distribution,
safer sex education, legal clean needle purchase, and needle exchange
programs are all examples of harm reduction strategies (84).
While injection drug use has a direct role in transmission
of HIV, noninjection drugs and alcohol can play a potent role as
cofactors of transmission because of their effects on behavior and
cognition. The treatment success of substance use disorders varies,
and the situation is further hampered because access to substance
abuse services is often limited or is unwanted; relapses are common.
Nonetheless, keeping substance use disorder intervention high on
the list of treatment priorities is recommended for persons at risk
for HIV infection.
One component of a comprehensive approach to HIV prevention
among injection drug users is access to sterile syringes. The U.S.
Public Health Service recommends that injection drug users who continue
to inject use sterile syringes to prepare and inject drugs and obtain
those syringes from a reliable source (e.g., a pharmacy). At the
same time, a wide variety of laws and regulations restrict the ability
of injection drug users to purchase and possess sterile syringes
(7). Numerous national organizations, including the American Psychiatric
Association (85), the American Medical Association, and the American
Pharmaceutical Association, have recommended in policy statements
and guidelines the removal of government restrictions on the availability
of sterile syringes and have supported government-sponsored needle
exchange programs. Cleaning drug injection equipment with bleach
is an alternative that requires a multistep cleaning process that
is impractical for many injection drug users (86).
Rates of HIV infection among psychiatric inpatients averaged
7.8% in seroprevalence studies conducted in East Coast
cities (87). Men and women were equally affected, with the highest
rates occurring among patients who were under 40, were black or
Latino, or used substances, especially injected drugs. Rates for
other geographic areas in the United States were not available.
Despite not identifying themselves as gay, 10% of
men with schizophrenia have reported same-sex sexual encounters
(88). Public mental health systems should implement prevention policies
and practices, educate both mental and medical health care clinicians
about key treatment issues, and develop effective linkages between
clinicians and systems of care (89, 90).
Severe mental illness may be associated with health risks
due to poor access to health care or decreased capacity to care
for oneself. Despite the challenges that chronically and severely
mentally ill patients face, risk reduction programs tailored to
their needs have been shown to reduce risk of HIV infection (91, 92).
Psychiatrists frequently encounter child, adolescent, and
adult psychiatric patients who have histories of being sexually
abused, including when treating patients with posttraumatic stress
disorder (PTSD), dissociative disorders, and borderline personality
disorder. Victims of sexual crimes vary from those with long abuse
histories to those with a single sexual assault. Sexual coercion
often results in long-term emotional damage to those that have been
assaulted and may be followed by PTSD or other psychiatric disorders.
These emotional scars are associated with increased vulnerability
to other HIV-risk situations.
A patient with a history of sexual abuse or trauma should
be asked about specific behaviors that are associated with risk
for HIV transmission. Patients with such a history may be reluctant
to provide information initially. Psychiatrists should determine
if a psychiatric disorder is present and whether treatment is indicated.
In the case of sexual assault, psychiatrists should expediently
gather enough information so that the decision about the appropriateness
of postexposure prophylaxis can be made (93).
The development of a psychiatric treatment plan for patients
with HIV infection requires thoughtful and comprehensive consideration
of the biopsychosocial context of the illness. Treatment decisions
must balance standard recommendations for psychiatric
conditions against the medical stage of HIV illness and up-to-date
information about available medical interventions targeted at the underlying
HIV infection. At the same time, psychiatrists should be aware that
emotional reactions and conflicts can interfere with a patient's
ability to follow medical recommendations and thus have a profound
effect on physical status. Psychiatrists should carefully consider
possible medical causes of psychiatric symptoms and whether a medical
workup is indicated to rule out a potentially life-threatening illness
due to HIV or HIV-related illness. Organ malfunction, synergism
of side effects of drugs, and drug-drug interactions are important
factors to address in the management of patients.
Establishing an alliance involves, in part, recognition of
a patient's understanding of his or her stage of illness
and an evaluation of how he or she is coping with it. The exploration
of cultural/ethnic beliefs regarding psychiatric and HIV
illnesses can also contribute to the formation of a solid alliance.
Because of the potential for the patient to feel shame and stigma
associated with HIV infection and the sensitive nature of discussing
risk behavior, psychiatrists should be supportive and not judgmental
to encourage trust.
Issues of confidentiality should be reviewed with the patient,
and the patient should be asked to consider the psychiatrist's
role in assisting with the process of disclosure of HIV status to
appropriate persons (94). In establishing a therapeutic alliance,
it is important to discuss with the patient whether he or she wants
to extend the treatment relationship to include selected communication
with the family or significant other(s). Lastly, given the importance
of the therapeutic alliance and the emotional impact of issues related
to HIV, the psychiatrist should be aware of transference and countertransference
feelings as well as personal attitudes about HIV infection and how
the patient acquired the virus.
Managing the health care needs of a patient with HIV infection
can be challenging due to the complex nature of the illness. Psychiatrists
must be aware that the illness changes over time and has many different
clinical manifestations. In addition, because information about
HIV-related treatment is constantly evolving, psychiatrists may
feel that their fund of knowledge about the most current interventions,
such as antiretroviral medications, is inadequate. To keep up to
date and to provide good clinical care, it is essential to collaborate
with other physicians in infectious disease, primary care, and other
Discussions of drug-drug interactions and the close monitoring
and workup of unexplained somatic or psychiatric symptoms are examples
of how psychiatrists and primary care physicians can assist each
other in providing high-quality comprehensive care. Patients should
specify their agreement for the exchange of specific information
between the psychiatrist and other clinicians in a written release
of information. It is often appropriate to use a multidisciplinary
team approach when managing a patient with HIV, especially as the
disease becomes more advanced. Access to both general medical and
specialty care may need to be addressed.
A number of surveys of persons with HIV infection have shown
an elevated premorbid rate of psychiatric disorders when compared
to rates in the general population. In addition, psychiatric disorders
can develop during any stage of HIV illness.
Psychiatric treatment of patients with HIV infection should
include active monitoring of substance abuse, since it is often
associated with risk behaviors that can lead to further transmission
of HIV. Clinicians must not assume that patients who have relatively
good immune functioning have no risk for CNS HIV disorders. Thorough
evaluation and accurate diagnosis are key to selecting
the appropriate intervention, whether it is risk reduction
counseling, neuropsychological testing, or the use of psychotropic
and antiretroviral medications.
There are no data to suggest that the psychotherapeutic management
of patients with HIV infection should be different from that of
other patients. Many clinicians use a variety of approaches (e.g.,
both time-limited and longer-term individual and group
psychotherapy) and psychotherapeutic models (e.g., cognitive behavior,
supportive, interpersonal, or psychodynamic/psychoanalytic).
Adherence to a treatment regimen is profoundly important for
patients with HIV infection. Research has demonstrated that less
than 95% adherence to antiretroviral medications results
in the development of viral resistance (95). Translated into actual
practice, if medication doses are taken twice a day, a patient cannot
miss more than one dose every 10 days.
Because comorbid psychiatric disorders, such as substance
abuse or depression, have been shown to adversely affect patients' compliance
with a complicated treatment regimen, psychiatrists and patients
should actively discuss adherence to both psychotropic and HIV medications
(96). Psychoeducational approaches are especially useful, since
they reinforce the importance of adherence, support appropriate
help-seeking, and identify barriers to adherence. Some
patients who are unable to modify their behavior after educational
approaches may be helped by intensive psychodynamic psychotherapy.
If indicated, outreach efforts with public health nurses and services
can be used to provide adherence assistance.
Mental health problems can occur at any stage of HIV illness
(e.g., around the time of serologic testing) (97), or they could
be precipitated by the onset of somatic symptoms. Preexisting
psychiatric disorders or personality traits may be exacerbated by
the onset of HIV illness. Patients may seek mental health services
on their own, but it is not uncommon for other clinicians to request
psychiatric consultation for patients who are in crisis or who have
psychiatric symptoms.
It is often the psychiatrist's role to educate other
clinicians and patients about the neuropsychiatric complications
of HIV infection and to initiate and encourage treatment of current
or emergent psychiatric disorders. When seeing a patient in consultation,
it is important to gather history about cognitive or motor symptoms
and conduct a mental status screening examination to determine whether
neurocognitive deficits are present (see Section III.B.2.a on screening
Psychiatrists are obligated to assess the risk for HIV transmission
from their HIV-infected patients to others and to provide
risk reduction counseling. This task should be a long-term treatment
priority, since many HIV-infected individuals continue risk behaviors.
Risk assessment should be repeated when there are changes in the
patient's clinical status or social situation, such as
the onset of binge drug or alcohol use or new sexual relationships.
Psychotherapy may help some individuals who are unaware of motivations
that promote ongoing risk behavior. When a psychiatrist cannot provide
the specific risk reduction intervention that is indicated for a
patient, he or she should refer patients to resources such as HIV/AIDS
service organizations and support the intervention when initiated.
Biomedical interventions have stemmed the progression of HIV
illness so that its course has increasingly resembled that of other
chronic medical illnesses. Therefore, maximizing psychosocial functioning
is relevant to the long-term social and economic impact of HIV infection.
Psychiatrists can enhance a patient's functioning by helping
him or her cope with the illness. Psychiatrists should ask about
and be aware of a patient's use of alternative or complementary
treatments, including herbal remedies.
Assessment of social supports, utilization of appropriate
community-based services, and resolution of financial and occupational
concerns are all potential fruitful domains of inquiry. Many patients find
support groups for persons with HIV infection helpful in coping
with their illness, whereas others may prefer individual, couples,
or family therapy.
Inquiry about the spiritual beliefs and religious faith of
a person with HIV infection should be a regular part of a psychiatric
assessment and treatment planning, since they can be an important
source of support for many with HIV/AIDS. Facing a serious
illness often serves as a catalyst for a search for meaning and
a renewal of spiritual beliefs and practices. A person's
religious history includes not only current beliefs and practices
but also religious traditions of one's family of origin
and ethnic culture.
Religious congregations have had different, sometimes negative,
responses to the spiritual needs of members with HIV/AIDS
that often correspond to the core beliefs of the faith communities
(98). Many ethnic minorities find the religious community or body
of the church to be the network that most effectively addresses
their need for support in crises.
The concept of spirituality goes beyond religious considerations
to encompass multidimensional and existential perspectives that
are important in maintaining well-being for many persons with HIV infection.
It is not uncommon for persons with HIV/AIDS to seek alternative
modes of spiritual expression, such as meditation. An assessment
of the spiritual needs of a patient involves questions around the
person's concept of God, sources of strength and hope,
significance of practices and rituals, and perceived relationship
between spiritual beliefs and health status (99). Information gathered
may help caregivers assist patients to better cope with their illness
at all stages but particularly as a patient nears death.
As HIV illness advances, a psychiatrist may be asked to help
evaluate the need for reasonable work or school accommodations or
the ability to return to work in line with the Americans With Disabilities
Act. Patients with minor children may need assistance with disclosure
of illness and the establishment of a custody plan in the event
of parental death from AIDS. Psychotherapy may be very helpful in
reducing the emotional distress and turmoil activated by approaching
The fundamental right of a patient with advancing HIV illness
to make treatment decisions can be supported when issues relating
to disability, death, and dying are discussed by the appropriate parties
in a timely and ongoing fashion. Discussions about preferences for
care should be initiated by physicians, since it has been reported
that only 36% of patients with AIDS had spoken with their physician
about their preferred treatment (100). It is recommended that patients
with HIV infection draw up a living will to guide end-of-life decisions
in addition to a durable power of attorney. Copies of these documents
should be placed in a patient's medical charts and in the
files of their primary and specialty physicians.
The HIV patient's significant otherspartner,
family, and friendsare often collaborative partners in
care and support who often shoulder a significant share of the clinical
day-to-day care of an acutely or terminally ill patient with AIDS.
They also are a rich source of collateral information about the
clinical status of the patient. The psychiatrist needs to take care
that the patient has given consent before speaking directly with
family and significant others.
Intimate involvement with the patient and his or her illness
can lead to mental health difficulties for the significant
others as well. Referral to support groups for significant
others affected by HIV may be helpful, as can encouragement to participate
in HIV/AIDS advocacy organizations. Both can provide emotional
validation and a degree of respite for a significant other. Some
significant others and family members may be best served by referral
for psychiatric evaluation and treatment, including individual
or family therapy.
Cognitive complaints are not uncommon among psychiatric patients
in general, but the evaluation of such complaints in a patient with
HIV infection requires a comprehensive psychiatric assessment, formulation
of a differential diagnosis, and possible medical workup. Symptoms
of early cognitive changes due to HIV can be subtle and can differ
from symptoms associated with cortical dementia such as Alzheimer's.
For example, HIV-associated dementia, due to its subcortical localization,
more commonly presents with psychomotor slowing rather than deficits
in language or visual recognition. Psychiatrists need to be aware
of these differences in clinical phenomenology in order to identify HIV-associated
dementia at early stages.
The widely used Mini-Mental State (101) is not sensitive in
picking up early HIV-associated cognitive motor symptoms. Alternative
screening examinations have been proposed that identify symptoms
more likely to be present with subcortical dementia (102–105).
Psychiatrists should become familiar with the available screening
examinations for cognitive motor impairment that are more specific
for subcortical symptoms (Table 14). It has been found that patient
self-assessment of cognitive status is not reliable (106). Therefore,
psychiatrists should administer a baseline screening examination
on every patient with HIV infection and plan to readminister the
test on a regular basis as part of the treatment plan. If there
is evidence of early cognitive impairment, formal neuropsychological
testing is useful to more comprehensively document cognitive dysfunction
as well as areas of relative cognitive strength.
Mental Alteration Test (102102)
Clinician administered
Timed test; verbal version of the Trail
Making Test; alternates between numbers and letters
HIV Dementia Scale (103103)
Five sections cover memory registration,
attention, psychomotor speed, memory recall, and construction
Executive Interview Test (104104)
A 10-minute, 25-item bedside test of
executive function, including snout reflex, word fluency, echopraxia,
go/no-go task
Once cognitive deficits are identified, the psychiatrist should
work in collaboration with infectious disease specialists, neurologists,
or primary care clinicians to develop a plan for further workup.
A magnetic resonance imaging scan often reveals no abnormality in
patients with early dementia, so this technique is not useful in
providing specific confirmation of HIV-associated dementia. The overall
immunological status of the patient should be assessed if not already
Pharmacologic treatment of HIV-associated dementia consists
of intervening with potent antiretroviral therapy that targets the
underlying HIV infection with consideration of whether the agents
adequately penetrate the CNS. For comorbid conditions such as depression,
psychiatrists should consider prescribing antidepressant medications
as they would for other medically ill patients. Last, for management
of symptoms associated with HIV-associated dementia (e.g., agitation
or fatigue), medications such as antipsychotic or stimulant agents,
respectively, should be considered.
Psychotherapy may be helpful for patients with mild to moderate
dementia in order to help them understand, mourn, and adapt to this
new impairment of functioning. Both medications and psychotherapy
can thus improve the quality of life both for persons with HIV-related
cognitive disorders and their significant others while also improving
overall clinical outcomes.
The evaluation of the cause of delirium in an HIV-infected
patient requires the psychiatrist to be alert to multiple possible
etiologic factors and be knowledgeable about specific diseases that
are associated with HIV infection. Examples are hypoxemia due to Pneumocystis
carinii pneumonia, uremia due to HIV nephropathy,
or elevated ammonia levels due to cirrhosis. One of the most important
factors is the multiple medications that HIV patients typically
take, which often cause delirium or contribute to delirious states
because of drug-drug interactions. Problems arising from such toxicity
are often reversible. Patients with AIDS who reside in either nursing
homes or assisted living facilities or who have been hospitalized
and who develop delirium have been shown to have significantly shorter
survival than AIDS patients without delirium (107, 108). HIV-associated delirium
may present with symptoms that resemble classic mania or drug intoxication,
thereby bringing patients to the attention of a psychiatrist for
evaluation. Delirium in the context of HIV infection should be evaluated
like delirium with other medical conditions (47). A psychiatrist
should advocate for a complete medical/neurological evaluation
for patients with HIV infection who present with an acute onset
of psychiatric symptoms with no previous psychiatric history. A
complete workup should include a toxicology screen, thorough neurological
examination, laboratory evaluation, and brain imaging studies. A
comprehensive assessment for infectious processes should be conducted and
may entail lumbar puncture.
Management of delirium in the context of HIV infection includes
judicious use of antipsychotic medications for symptoms of agitation
or perceptual abnormalities such as hallucinations. Many clinicians
use the newer, atypical antipsychotic agents due to their lower
side effect profile.
The management of disturbances in mood such as depression
or mania for patients with HIV infection is similar to that for
other patients with medical comorbidity. Fatigue and insomnia, frequent complaints
in otherwise asymptomatic patients, are likely related to psychological
disturbances such as major depressive disorder (109). In addition,
the overall medical status of the patient should be assessed to
take into account possible effects of concurrent illness or side
effects of medications such as efavirenz. Psychiatrists should know
all medications that a patient is taking. Choice of an antidepressant
or mood-stabilizing agent may be influenced by the antiretroviral
regimen in place, and doses may need to be adjusted if drug-drug
interactions are likely. Psychotherapy should be recommended when
Manic syndromes are difficult to treat in HIV-infected patients
for several reasons. First, mania may result from HIV infection
(secondary mania) (33), AIDS-associated brain infections, neoplasms, or
treatment with medications like steroids. In addition, manic syndromes
can be related to comorbid substance use disorders, and case reports
have documented manic symptoms induced by the antiretroviral agents
didanosine and zidovudine (110, 111). Patients who experience their
first manic episode later in the course of their HIV disease are
less likely to have personal or family histories of mood disorders
and are more likely to have dementia or neurocognitive slowing (34).
Although the prevalence and incidence of mania associated with HIV
are not well described, treatment studies suggest that traditional
antimanic agents are effective and tolerated.
In the United States, substance use disorders are prevalent
in the population of persons with or at risk for HIV infection,
and treatment is a high priority. Because drug- and alcohol-dependent
HIV-infected patients form a large reservoir for HIV in the United
States, and because behavior that risks transmission of HIV is often
associated with concomitant substance use, psychiatrists should
be aware that by treating substance abuse, they may well be preventing
HIV infection (112). Unfortunately, the number of injection drug
users in the United States outnumbers the available treatment slots.
Treatment with methadone or LAAM (113) can be an important
treatment component for persons with opiate dependence. Since the
quality of such programs varies, psychiatrists should help identify the
best program for their patients. Factors that often indicate higher
quality include the use of higher doses of methadone or LAAM and
a close working relationship with primary medical clinicians and associated
psychosocial services. It should be noted that doses of methadone
may need to be increased or decreased in accordance with the use
of specific antiretroviral agents that can have an impact on the
metabolism of methadone.
Psychiatrists may be primary providers of care in a variety
of clinical settings for HIV-infected patients who also have a substance
use disorder. Psychiatrists should either provide treatment for their
patients with comorbid substance abuse or collaborate with high-quality
substance abuse programs. Substance use disorders themselves are
often associated with comorbid psychiatric disorders such as anxiety,
depression, and psychotic symptoms. Treatment of these comorbid conditions
can help stabilize patients who are attempting to achieve sobriety
or abstinence.
Many problems involving anxiety symptoms can arise in relationship
to HIV illness. An example of a clinical anxiety problem without HIV
infection is AIDS phobia. For persons infected with HIV, there are
numerous points at various stages of the illness when anxiety about
the future, physical symptoms, or clinical decisions can become
overwhelming. Psychotherapeutic approaches to situational anxiety
can help patients work through intense affects and provide a structure
within which sound decisions can be made.
Anxiety disorders can precede HIV infection or arise as its
consequence. Treatment of anxiety disorders among HIV-infected patients
has not been well studied; thus, psychiatrists should apply standard
pharmacologic treatments for anxiety disorders with caution. For
instance, many benzodiazepines are contraindicated when patients
are taking protease inhibitors, particularly ritonavir, since predicted
pharmacokinetics suggest blood levels of these psychotropic agents
will be greatly elevated. Thus, benzodiazepines should be given
as a short-term intervention in most instances. Psychiatrists may
need to adjust medication doses and consider medical setbacks when
treating patients with prominent anxiety symptoms. Psychotherapy
may be effective in managing anxiety while reducing the need for
medications. PTSD is a possible outcome of sexual assault or abuse
and may be a focus of clinical treatment for some patients with
HIV infection.
Psychotic symptoms in the context of HIV infection, particularly
at advanced stages of illness, do not necessarily indicate a primary
psychotic disorder, such as schizophrenia, but may arise from causes
ranging from opportunistic infections, mania, HIV-associated dementia,
or delirium. Evaluation of new-onset psychosis requires a careful
medical/neurological workup.
There is no literature to suggest that the use of antipsychotic
medication needs to be modified for HIV-infected patients who have
good immune functioning and are not taking antiretroviral medication.
For patients taking antiretroviral medications, it is important
to be aware of drug-drug interactions and overlapping toxicities.
In particular, the use of clozapine is problematic with both ritonavir
and zidovudine, the former because ritonavir may elevate blood levels
of clozapine, the latter because clozapine and zidovudine can each
cause significant bone marrow suppression.
In late-stage HIV infection, atypical antipsychotic medications
are the first-line treatment because standard neuroleptic medications
have been associated with very severe and difficult-to-treat extrapyramidal
side effects. Also, in late-stage HIV illness, the lowest effective
dose of any atypical antipsychotic medication should be given, since
lower doses are sufficient to achieve efficacy and necessary to
help prevent side effects.
These disorders are interspersed among other diagnostic categories
and are differentiated on the basis of onset after an identifiable
stressor. Adjustment disorders are associated with significant emotional
or behavioral symptoms. Although they may arise from stressful life
events such as testing HIV-antibody positive, they may indicate
a subsyndromal state that will evolve into a severe psychiatric
disorder if left untreated. Various forms of psychotherapy may be
indicated to prevent progression to a more severe psychiatric disturbance.
Sleep complaints are common in HIV patients in psychiatric
treatment. Sleep disturbances may arise from a psychiatric disorder
such as depression or stem from complications of HIV infection. For
instance, because pain is a frequent accompaniment of HIV-related
illness and is often treatable, clinicians should intervene to alleviate
pain that causes sleep disturbance. The antiretroviral medication
efavirenz is associated with a high incidence of vivid dreams and
The presenting psychiatric problems of HIV illness in children
depend upon factors such as the age and developmental stage of the
child, HIV clinical stage, psychosocial situation, and individual vulnerabilities
for psychiatric disorders. Although there are few studies in this
area, psychiatric disorders are common among infected youth, with
rates of about 30% for mood disorders and 25% for
attention deficit hyperactivity disorder (114, 115). As mood and
anxiety disorders are more likely to be overlooked by caregivers
than disorders with prominent behavioral manifestations (externalizing
disorders), extra vigilance is required by the psychiatrist.
Just as the standard of care for HIV intervention has changed
for adults, so have the treatments for children infected with HIV.
Children have increased survival rates and slower progression to AIDS
with the use of antiretroviral medications.
Psychiatrists, especially child and adolescent psychiatrists,
need to help support children who survive to adolescence to negotiate
this complex developmental stage. Psychotherapy may be of particular
help for adolescents who are dealing with issues of developing sexuality.
For some adolescents, sexuality may be a reminder of their infection.
For others, sexual risk behavior may be a reenactment of parental
behaviors, a method of mastering their trauma, or a response to
their anger concerning their ill health. Substance abuse is frequent
(33% in one study) and is likely to involve multiple drug
use (116). The issues of risk behavior and autonomy have implications
for HIV prevention, adherence to treatment, and effective coping
with chronic illness. The family's understanding and capacity
to respond in a supportive manner are essentialthese adaptations
will not only help the child or adolescent cope with the attendant
biopsychosocial adversity, they may also influence morbidity and
mortality. The importance of family dynamics for children and adolescents with
chronic illness and handicapping conditions has long been recognized
(117, 118).
In the case of somatic syndromes that exist at the interface
of medical and psychiatric disorders, psychiatrists can serve to
integrate treatment approaches and promote interdisciplinary and
interspecialty dialogue. Symptoms such as fatigue, weight loss,
pain, and sexual dysfunction can be associated with HIV illness
as well as psychiatric disorders. It is useful to avoid all-or-nothing,
mind or body, approaches when evaluating such nonspecific symptoms.
Good communication between psychiatrists and other physicians leads
to better treatment decisions. Principles of palliative care apply
when a patient is terminally ill and desires treatment that focuses
on comfort and symptom relief.
Wasting syndrome generally occurs in patients with more advanced
HIV illness and can be related to a number of physiologic disturbances,
such as progressive HIV disease, hypogonadism, and gastrointestinal
malabsorption. Loss of lean body mass is a strong predictor of increased
mortality due to AIDS (119). Wasting is defined as loss of >10% of
ideal body weight.
Fatigue is a common, often chronic symptom in HIV disease,
frequently associated with depressed mood and physical disability,
particularly among patients with more advanced HIV infection or
Patients report pain at all stages of HIV illness, but complaints
tend to be more frequent and more intense at advanced stages of
systemic illness (123, 124). Common painful symptoms stem from headaches,
herpetic lesions, peripheral neuropathy, back pain, throat
pain, arthralgias, and muscle and abdominal pain (125).
Sexual dysfunction has been reported to occur in both men
and women with HIV infection. In men, hypogonadism can be treated
with testosterone replacement (126). As a rule, testosterone more effectively
treats diminished libido than erectile dysfunction.
AIDS and HIV infection disproportionately affect both the
African American and Hispanic populations in the United States.
In 1998, African Americans accounted for 45% of AIDS cases reported
that year while constituting only 12% of the total U.S.
population. The same year, the rate of reported AIDS cases for Hispanics
in the United States was 20%, although Hispanics constituted only
13% of the general population (Figure 5). In 1998, African
Americans overtook whites as the group with the largest number of
persons living with AIDS. The rates have been relatively constant in
the Asian/Pacific Islander and American Indian/Alaska
Native groups: about 1% of cases (Figure 6).
The statistics are even more skewed when classified according
to both race and gender. For those
cases of AIDS reported through 1998, 77% of all women with
AIDS were black or Hispanic; 81% of all children with AIDS
were black or Hispanic (127).
Three interrelated issues seem to account for the high rates
of HIV/AIDS in minority communities: 1) inequities in the
general health status in economically disadvantaged minorities,
2) problems controlling substance abuse in minority communities,
and 3) the role of substance abuse in the spread of HIV sexually
and perinatally.
HIV prevention efforts must be tailored for specific ethnic/cultural
groups so that their effectiveness can be enhanced. This point is
highlighted by the high levels of stigma associated with gay or bisexual
activity in the African American and Hispanic communities. The impact
of religious beliefs (Pentecostal, Catholic) in these communities
may also affect HIV prevention efforts due to negative views of
Hispanics in the United States constitute a diverse group
of cultures and countries of origin. Surveys have found that exposure
to HIV varies in different Hispanic subgroups. For example, injection
drug use is more prevalent among Hispanics from Puerto Rico, whereas
the more common risk behavior for Hispanics who originate from Mexico,
Cuba, and South and Central America is unsafe sex among men who
have sex with men (128).
Throughout most of the earlier years of the HIV/AIDS
epidemic, men who had sex with men were disproportionately affected.
Although this group still constitutes the population with the highest AIDS
incidence (37% of new AIDS cases in 1998), through massive
prevention interventions, rates for men who have sex with men have
declined, whereas other exposure categories are increasing annually.
For example, in 1998, 12% of new AIDS cases were linked
to heterosexual transmission (127).
Evidence from HIV prevalence studies and risk behavior surveys
supports the need to continue HIV prevention efforts among each
generation of gay and bisexual men. There are cohort differences in
attitudes, behavior, and perceived risk in younger and older gay
and bisexual men. In one study of six urban counties, 5%–8% of
adolescents and young men between the ages of 15 and 22 who were
having sex with men were already infected with HIV (3).
Bisexual women have been reported to have significantly more
sexually transmitted diseases and HIV risk than heterosexual women
(129), and women who have sex with women constitute a group with
a combination of risks for HIV infection. In general, female-to-female
transmission is thought to be uncommon, although theoretically possible.
The CDC writes that "of the 347 (out of 2,220) women who
were reported to have had sex only with women, 98% also
had another riskinjection drug use in most cases" (130).
Women who have sex with women do need to know that exposure to mucous
membranes, such as the vagina or mouth, or to vaginal secretions
or menstrual blood could transmit HIV, especially if the concentration
of the virus is high (early or late-stage HIV infection).
The percentage of women with both HIV infection and AIDS has
been steadily rising over the past decade. AIDS cases among women
and adolescent girls rose 364% between 1991 and 1997. Trends
in HIV diagnoses showed a 3% decrease in men but a 3% increase
in women between 1995 and 1996. Heterosexual contact is the leading
risk category for women (38%), with 29% of cases
in women resulting from personal injection drug use (127).
The exposure category "other/not identified" represents
32% of AIDS cases in women (127). It is typical for more
recently reported cases to be classified as "other/not
identified," but after medical record review and investigation,
most cases are eventually attributed to one of the defined exposure categories.
African American and Hispanic women are disproportionately
affected, with AIDS rates 17 and 6 times higher, respectively, than
for Caucasian women. Despite the difficult socioeconomic conditions
many minority women live in, a recent survey of health concerns
among low-income women found that AIDS was ranked as the most important
concern (131).
There are issues that are unique to women and HIV/AIDS.
Male-to-female transmission is estimated to be eight times more
likely than female-to-male transmission (132). Sex differences in HIV
measurements such as viral load, side effects of antiretroviral
medications, and access to quality health care have all been documented
(133). These biological differences make recommendations for antiretroviral
therapies more uncertain for women. In addition, most clinical trials
of interventions to treat HIV infection have enrolled male subjects.
Women, particularly HIV-positive women, have psychological, psychosocial,
reproductive, and gynecological concerns that differ from men (134, 135).
AIDS has always had the greatest impact on Americans ages
25–44. For example, in 1996, almost 75% of persons
with AIDS were between the ages of 25 and 44; 21% were
over age 44, and less than 4% were between the ages of
13 and 24. More recent data have shown that one in four new infections in
the United States occurs in people younger than 22 years of age
Because of the impact associated with new medical therapies,
many people's lives have significantly lengthened, which
has led to older generations of persons living with HIV/AIDS.
For instance, currently one out of 10 AIDS patients in the United
States is over 50 years old; in Florida, one out of every six AIDS
patients is older than 50 (136).
The age of diagnosis for 11% of AIDS cases is 50
years or older, and the age of diagnosis for 3% of AIDS
cases is 60 years or older (127). However, there remains a common
misperception that HIV is not a risk for older people. Many HIV-related
symptoms mimic the effects of aging, so clinicians may be slow to
diagnose HIV infection in older people and fail to question their
older patients about risk behaviors (137). This is troublesome given
research findings that document that adults over the age of 50 are
up to one-sixth as likely to use condoms as people in their 20s
(138). A particular diagnostic challenge for mental health clinicians
treating HIV-infected older persons involves neurological symptoms,
for which the differential diagnosis of cognitive impairment should
be broadened to include dementias seen in older age.
According to data from the first national multisite HIV/AIDS
Mental Health Services Demonstration Program, of nearly 2,000 persons
with HIV/AIDS seeking mental health services, a majority were
socially and economically disadvantaged (i.e., marginally employed,
poor, relying on public assistance, or under- or uninsured) (139).
Almost half of the 2,000 patients treated in this program lacked
medical insurance, and for all patients median monthly income was
only $575. Other sources of economic information yield
seroprevalence data that suggest higher rates of HIV infection among the
poor. For example, among Job Corps participants (who are primarily
economically disadvantaged youth), HIV seroprevalence rates are
twice that of youth seen at adolescent clinics and eight times higher
than rates for similar age youth who apply for military service
Although HIV has historically disproportionately affected
urban areas, rural populations are increasingly at risk. Although
more drug-related risk behaviors are reported by residents of large metropolitan
areas, high-risk sexual behaviors have not been found to differ
significantly among urban and rural residents (141). However, one
recent study found rural low-income women less likely to use condoms
than their urban counterparts (142). When compared to urban dwellers
living with HIV/AIDS, rural inhabitants report significantly
lower life satisfaction, lower perceptions of social support
from family and friends, reduced access to medical and mental health
care, elevated levels of loneliness, more community stigma, heightened
personal fear that their HIV status might be disclosed by others,
and more maladaptive coping strategies (143).
Suicide, attempted suicide, and suicidal ideation are complex
clinical issues that may arise during the course of psychiatric
care for HIV patients (144). Studies in the 1980s, before antiretroviral treatments,
reported rates of completed suicide in HIV-positive men as high
as 66 times that of the general population (145–147). However,
more recent data show suicide rates only modestly elevated and comparable
to those in other medically ill populations (148), although perhaps
most elevated among men who have sex with men (149). A study among
U.S. military service applicants found suicide rates for both HIV-positive
and HIV-negative individuals that were only marginally more elevated
than those in the U.S. general population (150).
A number of risk factors for suicide in HIV patients have
been described. They include psychiatric morbidity such as substance
abuse (151, 152), antisocial personality disorder (153), family
psychiatric history and family history of attempted suicide (154),
and major depressive disorder. Numerous psychosocial factors have
also been identified, such as a history of multiple HIV-related
losses, lack of social support, loss of employment or insurance
coverage, painful and disfiguring physical deterioration, exhaustion
of financial resources, and reliance on public assistance (155, 156).
Recent evidence has shown that patients with greater levels
of "fighting spirit," a specific pattern of adjustment
to life-threatening illnesses, tend to have lower levels of suicidal
ideation. Evaluation of suicide risk and other violent acts is an
integral part of a comprehensive evaluation for HIV/AIDS patients.
Psychiatric treatments that promote greater adaptation to living
with HIV infection may lower the risk of suicide for many patients
There are unique features to bereavement in the context of
HIV/AIDS. Deaths from AIDS often disproportionately affect
specific segments of the U.S. population. For example, it is not
uncommon for a member of the gay community to have lost multiple
persons to AIDS. At the same time, a bereaved individual may himself
or herself be infected with HIV. Reports have suggested increases in
high-risk sexual behavior and suicidal ideation in partners of individuals
who have died of AIDS (157, 158). Bereavement is often compounded
by the fact that many people die from AIDS at a young age, out of
synchrony with the normal developmental sequence (159, 160).
Growing numbers of children will lose one or both parents
to HIV. Psychiatrists need to explore the capacity of families to
communicate about HIV and the children's understanding
of their parent's illness. Disclosure is difficult for
many parents who worry about revealing stigmatized behaviors or overwhelming
a child with information (161). Permanency planning is an essential
step in communication and collaboration with social agencies. For
many children, bereavement is complicated by the psychosocial problems
that existed before HIV that are then compounded by disintegration
of the immediate family. Problem behaviors in adolescents who anticipate
losing one or both parents to AIDS have been described (162). Family-based,
multidisciplinary team approaches may be effective in providing
access to care and needed follow-up services.
Researchers have studied the relationship of AIDS bereavement
and psychological or medical variables but have not necessarily
found that greater numbers of AIDS losses are associated with a higher
rate of depressive symptoms or depressive disorders (163) or that
distress increases in a dose-response relationship to the number
of losses (164). One investigation reported changes in measures of
immune function relevant to HIV disease in bereaved HIV-positive
men that suggested patterns consistent with disease progression
(165). Bereavement has been associated with decreased lymphocyte
proliferation (164, 166) and decreased natural killer cell function
(167, 168).
Group therapy is often recommended for AIDS-related bereavement
(169). Group participants include partners, friends, family, and
caregivers of persons who have died of AIDS. A randomized, controlled
trial of support group interventions for bereaved HIV-positive and
HIV-negative men demonstrated significant improvement in grief symptoms
for the treatment group compared to control subjects (170).
Several studies have reported that patients with HIV infection
have a prevalence of personality disorders in the range of 19%–37%,
which is higher than rates found in comparable patients who are not
infected (171). Personality disorders categorized (per DSM) within
cluster B, such as borderline and histrionic personality disorder,
are the most common (172). These data are supported by clinical reports
from settings that provide care for large numbers of HIV-infected
patients (173). The findings are not surprising given the association
between personality disordersespecially those disorders
in which "impulsivity" is prominentand
risk factors for HIV infection such as high-risk drug use and sexual
behaviors. Personality disorders among those infected with HIV are
associated with a higher rate of depression, maladaptive coping,
and other psychiatric symptoms (174, 175) as well as with a higher
rate of injection drug use (176). In fact, one study has documented
that among their sample of HIV-positive and "at risk" HIV-negative
gay men, persons with personality disorders were at significant
risk of onset of future axis I disorders and serious functional
impairment, regardless of a past history of axis I disorders (177).
No studies have assessed the efficacy of specific treatments
for personality disorders among individuals infected with HIV. There
is no evidence against the use of standard psychiatric treatments for
personality disorders, tailored to the individual patient. Some
clinicians use an approach that includes limit setting, especially
limits on the inappropriate use of medical resources and medications. Other
strategies for complex cases emphasize the development and maintenance
of a doctor-patient relationship, treatment of comorbid conditions
such as depression and substance abuse, and supportive or cognitive
psychotherapy techniques (173).
The relationship of behavior and psychopathology to immune
measures has been the focus of ongoing research over recent years.
With regard to HIV infection, the findings are mixed. On the one hand,
a number of studies have found that stressful life event burden
is associated with decreased CD4 cell count (178–180),
decreased cytotoxic T lymphocyte count (181), clinical HIV disease progression
(182, 183), and physical symptom burden (168). In contrast, the
relationship of variables such as stressful life events and depressed
mood levels with markers of immunological progression has not been
supported by other studies (184, 185).
There appears to be an increase in the frequency and severity
of depression around the time of the onset of AIDS that persists
throughout the time of severe immunodeficiency (66). Whether depressed mood
levels in general are associated with decreases in immune function
is not clear, since one study has shown such an association (186),
whereas another has not (187). The disparity across studies attempting
to elicit such natural history relationships may be due to methodological
differences related to the extent to which other factors, including
immunological measures and clinical disease progression, had been
controlled (179).
Interventions such as cognitive behavior stress management,
coping skills enhancement training, massage therapy, existential
therapy, bereavement support groups, and antidepressant medication have
all been evaluated with regard to their effect on immune measures
(188–190). The findings are mixed, with some interventions
showing modest improvements of specific immune measures, whereas
others did not result in positive changes. Most interventions are
safe, including those that involved the antidepressants fluoxetine
and imipramine (190). At this time, these types of interventions
should be regarded as investigational in terms of their immunological
and health effects. However, psychotherapeutic and psychopharmacologic
interventions are indicated for their alleviation of distress and
enhancement of functional status.
A caveat regarding the use of such interventions is that many
patients hold beliefs that may lead to inappropriate expectations
of the potential for immunological and clinical health effects.
Patients who do not observe these effects may come to blame themselves
(and their behavior) for the lack of such immunological and clinical
effects and for disease progression. This could actually
result in increased distress. Hence, patients must be carefully
prepared for understanding the context in which behavioral interventions
are being offered and which outcomes should be considered primary (psychological
and functional) and which might be considered secondary and investigational
(immunological and clinical health). On the other hand, clinicians
should not discourage use of adjunctive techniques that can potentially
add to the effect of current medical management by expanding the
comprehensiveness of care.
Alternative and complementary medicine is an important part
of the health care sought by many Americans. Surveys of the U.S.
public in both 1990 and 1997 demonstrated that over one-third of Americans
used at least one unconventional treatment in the past year, with
rates rising from 34% to 42% between 1990 and
1997. It is estimated that the number of visits to nontraditional
care clinicians exceeds total visits to all U.S. primary care physicians
and represents $27.0 billion in annual out-of-pocket expenditures
(191, 192). More than 60% of patients who use complementary/alternative
treatments do not disclose the treatments to their doctors. Depression
is one of the most common conditions for which patients seek alternative/complementary
Surveys specific to the HIV-infected population report similar
findings, with between 30% and 68% of respondents
reporting use of some form of complementary/alternative
treatment (193–196). Patients with HIV/AIDS use
complementary and alternative medicine to improve general health
or quality of life, prevent progression of HIV disease, treat specific
symptoms, or counter side effects that result from biomedical treatments
(197, 198).
According to data from the first 1,016 participants of the
Alternative Medical Care Outcomes in AIDS Study, the 10 most frequently
used activities are aerobic exercise (64%), prayer (56%),
massage (54%), needle acupuncture (48%), meditation
(46%), support groups (42%), visualization and imagery
(34%), breathing exercises (33%), spiritual activities
(33%), and other exercise (33%) (199). Other nontraditional
treatments include nutritional, vitamin, or herbal supplements and
medicinal use of marijuana and anabolic steroids. Only
one research study to date has examined complementary therapy in
the context of HIV infection. A multisite project is currently being
conducted in cooperation with the Office of Alternative Medicine,
National Institutes of Health, to evaluate these treatments (200).
Institutions that house, treat, or incarcerate have a responsibility
to address issues of HIV education, prevention, and clinical services
for persons served in these settings. Seroprevalence studies in
institutional settings identify the scale of HIV infection and help
inform policies for the institution. For example, concerns about
HIV infection among institutionalized mentally retarded persons
have been somewhat allayed by studies that found either no cases
of HIV infection (201) or low rates (0.16%) (202). These
institutions nonetheless need to maintain universal blood and body fluid
precautions as well as develop prevention programs tailored to their
patient population.
Some of the highest rates of HIV infection are found among
jails and prisons due to the high frequency of drug-related sentences
and high-risk behaviors that occur within the institutions. Prevalence
rates among male inmates have been recorded between 6% and
8.5% (203, 204); one study of incarcerated women in New
York found an 18.8% rate of HIV infection (205).
Despite the alarmingly high rates of HIV infection among prisoners
in the United States, administrative and institutional barriers,
such as not allowing the distribution of condoms, undermine prevention
interventions. Collaboration between institutional staff and clinicians
or researchers of HIV prevention efforts may lead to effective interventions
for inmates and their partners (206). Psychiatrists working
in correctional facilities may need to advocate for patients who
may not receive antiretroviral medications in a timely manner due
to lockdowns, solitary confinement, or other factors. Recommendations
for handling HIV-related issues in psychiatric institutions can
be found in policy and position statements issued by the APA Office
on AIDS (http://www.psych.org/aids; click on "Policy
HIV creates unique demands on clinicians. Stresses that are
associated with the care of HIV-infected patients include fear of
contagion, the emotional impact of dying patients, stigma associated with
AIDS, anxiety concerning sexual and drug risk behavior, a constantly
changing knowledge base, and often inadequate treatment resources
(207). Health care workers have numerous reactions to these stresses.
Clinicians have reported, for example, greater anxiety, more interference
with nonwork activities, and symptoms similar to PTSD when treating
AIDS patients as compared to non-AIDS patients (208, 209).
Despite the stresses and demands, most clinical staff members
feel positively about their work, and only a small minority experience
job burnout. The frequently cited rewards of working with HIV-infected
patients include a sense of personal helpfulness, increased professional
mastery, altruism, and admiration for patients' courage
(210). In order to support employees, most multidisciplinary programs
address issues that are likely to cause stress, such as death and
dying, the management of sexuality, and fear of contagion. Interventions
to address these issues range from weekly informal team meetings
to leader-based staff support groups (211, 212).
Workshops that allow caregivers an opportunity to express
grief, explore frustrations, and share resources may be helpful
(213). Progress in HIV therapeutics requires frequent educational
updates. Appropriate resolution of staff conflict and disagreement
is useful in the HIV care setting, as it is in other settings that
deal with chronic medical illness. One study, for example, found
that HIV health care workers who perceived colleagues as significantly
stressful were nearly 50% more likely to experience job
burnout (214). Thus, a well-functioning HIV team may help buffer
the stresses of providing care, and psychiatrists can be effective
by assisting those teams.
In a national survey of 417 practicing psychiatrists conducted
in 1997 by APA, the physicians reported that over 9% of
patients they treat are at risk for HIV infection (215); the rate
was derived from questions about psychiatrists' knowledge
of patient risk behavior. This estimate is probably conservative,
since many psychiatrists do not conduct a detailed HIV risk assessment.
Nonetheless, the survey data support other findings that psychiatric
patients report higher rates of HIV risk behavior than the general
population (141) and underscore the important role that psychiatrists
play in preventing HIV infection.
Studies of primary care clinicians who conduct HIV risk assessments
among patients who express concern about HIV risk found that in
73% of the encounters, the physicians did not elicit enough information
to adequately characterize patients' HIV risk status (216).
It is estimated that only two-thirds of all HIV-infected people
in the United States know their serological status. Hence, many
do not know until they are diagnosed with AIDS. The CDC recommends
routine voluntary HIV antibody testing of patients who are admitted
to hospitals that have HIV seroprevalence rates of >1% among
admitted patients.
A multistate evaluation found that anonymous HIV
testing was associated with earlier HIV testing and HIV-related
medical care when compared to those who were tested confidentially (217).
Concerns about HIV test confidentiality led to a study of testing
trends in six states that initiated name-based reporting of HIV
test results. The researchers did not find significant declines in
the total number of HIV tests performed at counseling and testing
sites other than those expected from trends present before name-based
reporting (218). Moreover, Osmond and colleagues (219) surveyed
nearly 2,000 HIV-seropositive patients diagnosed during 1995–1996
in five states with name-based HIV surveillance (and three without)
and reported that keeping records of people infected with HIV by
name does not help or hinder treatment.
Home collection testing for HIV provides a method for testing
among individuals who may not otherwise seek HIV testing through
publicly funded sites or medical providers. A review of data collected
by test manufacturers in the first year of availability (1996–1997)
reported that of 174,316 tests performed, 0.9% were positive.
Most users of home collection tests were white men aged 25–34
years; HIV prevalence was highest among nonwhites, men who had sex
with men (particularly bisexual men), and injection drug users.
Nearly 60% of those who submitted samples and 49% of those
who tested positive had never had a previous HIV test (220).
A wealth of literature addresses the issue of how to intervene
to reduce HIV risk behavior at both the individual and community
level. While this section will focus primarily on data concerning interventions
at the individual level, macro-level changes in structure or policy
can lead to powerful community-level support of specific behavior
changes (221). The AIDS Community Demonstration Project is a good
example of a community-level intervention. Community volunteers
and "small" media were able to influence community
norms about the use of condoms and disinfection of drug injection
equipment by using bleach (222). Other examples of societal-level
policies that influence the effectiveness of individual-level HIV
risk behavior interventions are 1) laws that prohibit same-sex marriage,
which hinder the establishment of long-term monogamous relationships
for men who have sex with men (223), and 2) insufficient substance
abuse treatment capacity, which decreases the opportunity for an
injection drug user to receive treatment.
Sexual behavior is the target of most prevention efforts worldwide,
but because of the diversity of sexual behavior and the influences
of economics, culture, and environment, interventions to stem HIV
necessarily vary as well (224). Because of the sheer size of the
prevention literature and the many specific populations that have
been targeted, these guidelines will not provide more detailed information
about subgroups based on gender, ethnicity, or age. A publication
from the CDC entitled "Compendium of HIV Prevention Interventions
with Evidence of Effectiveness" provides a useful synopsis
of the research in this area (225).
The HIV counseling and testing model has been widely used
in studies that intend to promote behavior change in persons at
risk for HIV infection. Yet, two large reviews of HIV counseling
and testing studies (226, 227) found that HIV counseling and testing
interventions do not consistently lead to risk reduction or promote
help-seeking behavior in most populations studied. Both analyses found
that serodiscordant heterosexual couples demonstrated the most change
in risk behavior. A recent meta-analysis of the effect of HIV counseling
and testing interventions found that they were more effective in
secondary prevention for HIV-positive persons than as a primary
prevention strategy (228).
The most widely used counseling models acknowledge that knowledge
about HIV transmission and prevention is necessary but not sufficient
for behavior change (229–231). More effective interventions
rely on skills training and take into account individual psychosocial
and cognitive strategies (232). Essential to effective counseling
is helping patients perceive themselves as at risk for HIV infection,
addressing motivation to reduce risk, and ensuring that patients
have the skills and resources to implement risk reduction strategies.
Changing peer norms with the help of peer leaders and matching the
background characteristics (e.g., race, ethnicity, sexual orientation)
of the leader to the targeted population often help increase intervention
The largest randomized, controlled HIV behavioral intervention
study conducted in the United States found that even among persons
served in public health settings, a small-group, seven-session risk
reduction intervention cut reported high-risk sexual behaviors in
half and more than doubled reported regular use of condoms (from
23% to at least 60%) (233). HIV prevention interventions have
proven useful for psychiatric populations, including injection drug
users and people with severe mental illness, and have been shown
to be effective even when conducted in busy public clinics (234, 235).
The principles for preventing the spread of HIV among active
drug injectors are similar to those used to modify unsafe sexual
behavior. Ethnographic research has clarified how injected drugs
are purchased, dissolved, filtered, transferred into syringes, and
injected, and how sharing practices at each step in the process
contribute to the potential spread of HIV (236). Successful interventions focus
on knowledge, motivation, and behavioral skills that are tailored
to realistic strategies for changing sharing practices. These programs
have also engaged members of the injection drug use community as
prevention leaders.
An international study found that injection drug users are
capable of changing their risk behavior and providing accurate reports
of their behavior. Further, these behavioral changes are associated with
lower rates of HIV infection (237). A review of the research literature
on HIV prevention outreach efforts concluded that most such programs
have led to changes in drug-related and sex-related risk behaviors
in injection drug users (238). Specific reductions in drug injection,
sharing of injection equipment, and crack use and increases in needle
disinfection, condom use, and entry into drug treatment were seen
with such programs.
The most controversial component of HIV transmission prevention
in the injection drug use population has been the use of needle
and syringe exchange programs that make sterile equipment available
to drug injectors. These programs have met strong political opposition
in many countries, including the United States, and assessment of
their effectiveness has been fraught with methodological difficulties.
There are unsubstantiated concerns that exchange programs may attract
subjects who engage in the riskiest practices and that the number
of needles or syringes in circulation may not be sufficient to ensure
single-time use (239). Recent U.S. and international data make a
strong argument for the benefits of needle exchange programs on
reducing HIV transmission as well as other parenterally transmissible
infections such as hepatitis B and C (240, 241). Nonetheless, since
federal funds to date have been prohibited for use in needle exchange
programs, they have had limited impact on lowering HIV transmission
in the United States. Needle exchange programs that do exist are
often small and cannot meet local demand.
Before interventions with antiretroviral treatment were instituted,
between 1,000 and 2,000 infants were born each year in the United
States with HIV infection (242). Since recommendations were made
for routine counseling and voluntary HIV testing of pregnant women,
and for subsequent treatment with zidovudine for those who prove
seropositive, the CDC has recorded dramatic decreases in perinatal
transmission. From 1992 to 1997, cases of perinatal AIDS declined
67%, including an 80% decline in AIDS cases among
infants and a 66% decline among children between the ages
of 1 and 5 (243). It has been shown that elective cesarean delivery
may further decrease the risk for fetal infection (244).
The protocol of administering zidovudine to a pregnant woman
in the last two trimesters, followed by intravenous zidovudine during
delivery, then 6 weeks of zidovudine treatment for newborns was found
to reduce the incidence of HIV transmission from mother to child
from 22.6% to 7.6%a 66% reduction
(245, 246). While the mechanism by which zidovudine reduces perinatal
transmission is not known, research has shown that a risk factor
for perinatal transmission is the amount of HIV in the pregnant
woman's blood (247, 248). At the same time, the effect
of zidovudine's lowering maternal HIV viral load does not
fully explain the efficacy of zidovudine in reducing transmission. Another
important component of protection may be preexposure prophylaxis
of the fetus or infant to antiretroviral drugs. Because it has been
shown to be metabolized into its active triphosphate form within
the placenta, zidovudine may have distinct superiority in efficacy
compared to other nucleoside analogues such as didanosine and zalcitabine
There have been other studies of interventions to reduce perinatal
transmission, such as short-course antenatal/intrapartum
zidovudine in non-breast-feeding Thai women (250) or the combined agent
lamivudine/zidovudine during gestation, intrapartum, and
postpartum in African women (251). Both interventions were associated
with reductions in perinatal transmission by approximately 50% (even
though the group given lamivudine/zidovudine breast-fed).
In the situation when the diagnosis of HIV infection is not made
until near the end of gestation or during labor, treatment with
the combined agent lamivudine/zidovudine or nevirapine
in the intrapartum/postpartum period has been shown to
be effective in reducing transmission (251, 252).
There are limited data on the effect of combination antiretroviral
therapies on pregnancy outcome. A retrospective Swiss study reported
that 80% of women experienced side effects to the drugs,
which included reverse transcriptase inhibitors and protease inhibitors,
and further, found a possible association with preterm birth (253).
Women who face decisions regarding the use of antiretroviral
medications during pregnancy must consider the effects of treatment
on their own health as well as on fetal or child health. These decisions are
complex, since the standard of care has moved to multiple antiretroviral
drugs, and yet the long-term consequences of exposure
to such drugs by the infant are not known. In general, the three-stage zidovudine
regimen (prenatal, intrapartum, and postpartum) alone or in combination
with other antiretroviral agents should be discussed and offered
to all HIV-infected pregnant women.
Antiretroviral protocols to prevent perinatal transmission
are burdensome for patients and practitioners, and adherence is
again a crucial factor in treatment effectiveness. A 1995 study
found that only 15% of HIV-positive mothers and their newborns
received the full zidovudine treatment regimen (252). This same
study found that 26% of pregnant women with HIV infection
did not receive any prenatal care. Coordination of care by providers
of medical, mental health, drug abuse, and social services may be
required for the successful implementation of antiretroviral treatment
during pregnancy.
While universal infection control precautions have become
the standard of care in the U.S. health care system, as of June
1998, 54 health care workers had documented HIV infection through occupational
exposure. Of the 54, 46 had percutaneous (puncture/cut
injury) exposure, five had mucocutaneous (mucous membrane or skin)
exposure, two had both percutaneous and mucocutaneous exposure,
and one had an unknown exposure (82). The estimated risk of HIV
infection in health care workers with percutaneous HIV exposure
is approximately 0.3% (254).
Postexposure prophylaxis with antiretroviral agents has been
shown to be safe and effective (82). The postexposure prophylaxis
protocol outlines specific steps in assessing risk. First, the type
of exposureincluding type of material, contact surface
type, volume, and severity of exposureis determined. Next,
the HIV status of the exposure source is assessed on the basis of
factors such as probable viral titer (based on clinical HIV status
of exposure source) and whether actual HIV status is known (it may
be unknown). The exact postexposure prophylaxis recommendationwhether
to intervene at all, use two agents (zidovudine and lamivudine),
or use three (both of the above plus either indinavir or nelfinavir)is
based on these assessments. If done properly, postexposure prophylaxis
can reduce the risk for occupational transmission of HIV infection
in health care workers with known exposure, such as a needle stick
injury involving blood or other body fluids, by 80% (255).
HIV is spread both by sharing injection drug use equipment
(most frequently practiced by opiate, cocaine, or methamphetamine
users) and by engaging in unsafe sexual practices that are associated with
substance use disorders. Documented sexual risk behaviors among
those with substance use disorders include having multiple partners
in the context of buying or selling sex for drugs or money to buy
drugs; unprotected sex with injection drug users; and difficulty
employing safer sex practices while intoxicated. These sexual encounters
can also increase the risk of transmission of other sexually transmitted
diseases that are cofactors for HIV transmission. Unfortunately,
sexual risk behaviors are more resistant to change than drug-use
risk behaviors in drug users (256).
Comorbidity of substance use disorders with other psychiatric
disorders deserves mention. A study that used data from the 1992
National Survey of Veterans examined whether substance abuse or
other mental disorders serve as risk factors for HIV infection.
The investigators found that the combination of substance abuse
and PTSD increased the rate of HIV infection by almost 12 times
over that of those without either disorder (257).
Drug use disorders are associated with high rates of incarceration
for drug-related crimes. Jails and prisons, in turn, bring people
with elevated rates of HIV infection together in a confined space, increasing
the chance that a sexual or injection drug use partner encountered
in these settings will be infected with the virus (258, 259). Institutionalization
in all-male settings also increases the likelihood of sex between
There are geographic differences in seroprevalence rates of
HIV in injection drug use populations, with the highest rates in
the United States occurring in the Northeast, on the East Coast,
and in Puerto Rico (3). Holding the risk behavior constant, the
likelihood of acquiring HIV increases with its penetration into
a given geographic area by increasing the chance that sexual and
drug injection partners will be infected. Because substance use
disorders are associated with decreased occupational functioning
or disability, many of these individuals become impoverished and
often cluster in urban neighborhoods that are endemic for HIV.
The severely and persistently mentally ill population is at
risk for HIV infection due to factors analogous to those of patients
with substance use disorders. There are high rates of substance
use disorders among those with severe mental illness, and both populations
share similar tendencies to reside in institutions or poor urban
neighborhoods where cases of HIV infection are concentrated. Chronically
mentally ill adults have been documented to have misunderstandings
about AIDS transmission, to have histories of treatment for sexually
transmitted diseases, and to report behaviors such as "survival
sex" (in exchange for shelter, food, or money) (260). When
compared to the general population, people with severe mental illness
have higher rates of same-sex sexual activity and intimate contact
with multiple partners (261). One study found an association of
positive symptoms of psychosis and the diagnosis of schizophrenia
with specific high-risk sexual behaviors (74).
Randomized, controlled trials of relatively brief AIDS prevention
programs for the chronically mentally ill led to significant improvements
in rates of unprotected intercourse and condom use (262) and knowledge
about AIDS (263) in the intervention groups. It is not known whether
such improvements persist beyond the short follow-up period.
A history of sexual abuse is highly prevalent among both women
and men living with or at risk for HIV infection. One report of
408 mostly economically disadvantaged women (at least 18 years old) found
a lifetime prevalence of sexual abuse of 43%; over one-half
of the cases occurred during adulthood (264). A cohort of 327 homosexual
or bisexual men had a 35.5% rate of childhood sexual abuse.
Men with a history of childhood sexual abuse reported more lifetime
male partners and a higher likelihood of unprotected receptive anal
intercourse in the past 6 months (265). Women with a history of
childhood sexual abuse have been found to have more sexual partners,
heightened sexual activity, and more negative expectations of condom
use (266). For example, a study of women in low-income housing developments
found that those with a history of sexual coercion were likely to perceive
that requesting a partner to use a condom would create a potentially
violent situation (267).
In children, the occurrence of sexually transmitted diseases
can be the first indication of sexual abuse. Although perinatal
transmission of HIV accounts for the vast majority of HIV cases
in children, HIV transmission has been reported to occur through
childhood sexual abuse (268). Efforts to encourage active risk reduction
in high-risk populations through AIDS education have found that adolescents
who have been sexually abused are significantly less likely to use
condoms and have much greater communication difficulties than their
peers (269).
Psychiatric treatments for individuals with HIV infection
follow the same principles as for any patient with a psychiatric
diagnosis, but there are special considerations. As with other patients
with comorbid medical and psychiatric illnesses, it is essential
to help patients cope with HIV illness and, when appropriate, with
death and dying. There is also an ongoing need to determine whether
new psychiatric symptoms have a medical basis that requires intervention.
Examples of unique treatment issues with HIV patients include but
are not limited to the following:
working with the patient
on disclosure of HIV status;
assessing dangerousness from the perspective of HIV
transmission and intervening to reduce that risk;
helping families with dependent children arrange permanency
treating HIV-infected children who have developmental
delays resulting from prenatal drug exposure or from HIV infection;
negotiating disability status and, for some patients,
a return to work;
bereavement/loss; and
treatment adherence.
Most patients are asymptomatic for many years after becoming
infected. But once symptomatic with more advanced HIV disease, they
may become high users of medical care, including mental health services
(270). They may need frequent assessment and treatment visits, undergo
many medical tests, require hospitalization, and take multiple medications
(often as many as 10–15 different medications at different
times of day). Many patients receive medical care from an HIV primary
care or infectious disease clinic or from an infectious
disease specialist in the community. A recent study reported better
medical outcomes for patients with HIV infection who receive care
from physicians with more experience treating HIV diseases
The Ryan White CARE (Comprehensive AIDS Resources Emergency)
Act was enacted in 1990 to help states, communities, and families
provide care for people with HIV/AIDS who lack adequate health
insurance or other resources. Since its inception, CARE Act grants
have totaled $6.4 billion and have served approximately
500,000 individuals with HIV/AIDS annually. Administered
by the Health Resources and Services Administration of the U.S.
Department of Health and Human Services, CARE Act grants were reauthorized
in 1996 and comprise several programs. Title I grants provide funds
to cities for low-income or under- or uninsured persons to cover
the cost of health care and medications, as well as support services
like counseling and home and hospice care. Title II grants are for
the 50 states, the District of Columbia, Puerto Rico, and U.S. territories
to improve the quality, accessibility, and organization of both
health care and support for patients with HIV/AIDS. Title
III grants are given to public or nonprofit entities that provide
comprehensive primary health care services for persons with AIDS
or at-risk populations. Title IV grants fund efforts to coordinate HIV
services and access to research for children, youth, women, and
families. An additional component of the CARE program includes training
for health care professionals, grants for innovative service delivery
models for special populations, and dental services.
Despite CARE Act funding, lack of access to care remains a
problem that affects morbidity and mortality for certain groups.
One study documented that among urban patients who receive medical care,
there are no differences in HIV disease progression or survival
associated with sex, race, injection drug use, or socioeconomic
status. This suggests access to medical care is a main determinant
of how quickly a patient develops AIDS (272). More recently, investigators
from the HIV Cost and Services Utilization Study, a national population-based
sample, found that African American, Hispanic, female, uninsured,
and Medicaid-insured individuals all had inferior patterns of medical
care (e.g., later initiation of antiretroviral medication) than
did Caucasian and privately insured individuals (273).
Persons with HIV infection have higher rates of most psychiatric
disorders than the general population. Psychiatric patients with
common medical problems, especially those with severe mental illness,
receive suboptimal medical care and suffer greater morbidity and
mortality from medical illnesses than the general population. Studies
are now under way to determine the access of patients with severe
mental illness to HIV-related medical treatments; it can be assumed
that these patients need help to access medical services.
Psychiatric disorders can be underdetected, misdiagnosed,
undertreated, or treated improperly in primary care settings. For
example, while a substantial majority of HIV-infected persons presenting for
intake to an HIV primary care clinic suffered from depression, substance
dependence, or another current psychiatric disorder, most cases
were not detected by clinicians (66). Underscoring the importance
of mental health care is the finding that ongoing high-risk sexual
behavior is predicted by higher levels of depression and recreational
drug use (274).
There are several patient barriers to meeting the mental health
needs of HIV-infected persons. These barriers include
adherence difficulties (e.g., missed appointments or inability to
follow treatment recommendations); fear of additional stigmatization
(the "double stigma" of HIV and a mental disorder);
negative prior experiences with the mental health system; lack of
funds for transportation, payment of care, or medications; unstable
housing and frequent relocation; and the complex comorbid presentations
of patients with HIV infection (e.g., depression complicated by concurrent
substance dependence and a personality disorder). On the other hand,
health care professionals should not assume that depression is "normal" in
a person with HIV infection.
Some innovative HIV clinics integrate medical, mental health,
and substance abuse treatment within their programs (275). These
model programs increase the opportunities for prevention and treatment
and may reach a more impaired population (276). One model uses an
outpatient psychiatric consultation-liaison clinic that specializes
in the treatment of HIV-infected patients. The clinic can be physically
off-site from an HIV clinic but receives most of its referrals from
that clinic. Other models include HIV programs within community
mental health centers, programs located within residential substance
abuse treatment facilities, freestanding community-based agencies,
and referrals to private practitioners with expertise in treating
HIV patients. All of these models appear to be effective (67).
In general, the use of psychotropic agents in HIV patients
follows similar principles for using these medications in such populations
as geriatric patients or those with comorbid medical illnesses.
This is particularly true for patients with more advanced HIV disease
and those on complex antiretroviral regimens who may be more sensitive
to medication dosages and side effects and are at higher risk for drug-drug
interactions (277). Because some standard medications used to treat
HIV infection or HIV-related conditions can potently inhibit
or induce the cytochrome P450 system, psychotropic medications that
share metabolic pathways should be used judiciously; however, this
concern should not preclude appropriate pharmacologic intervention.
General guidelines, particularly for patients with symptomatic
HIV disease, include 1) using lower starting doses and slower titration,
2) providing the least complicated dosing schedules possible, 3)
focusing on drug side effect profiles to avoid unnecessary adverse
events (e.g., anticholinergic effects from tricyclic antidepressants, leukopenia
from carbamazepine), and 4) maintaining awareness of drug metabolism/clearance
pathways to minimize drug-drug interactions and possible end organ
Published reports of adverse events and side effects can offer
specific guidance for the use of some psychotropic agents in HIV-infected
patients. However, clinicians must be cautioned that many studies
that have examined psychotropic effectiveness in HIV patients were
conducted on relatively asymptomatic patients, often did not include
women or youth, and were conducted before the availability of combination
antiretroviral therapy. Liver disease, in particular hepatitis C,
is becoming increasingly important as a comorbid condition. Thus,
routine liver function testing is necessary when prescribing psychotropic
medications for patients with HIV infection.
Combination therapy with multiple medication classes constitutes
the standard of care for successful treatment of HIV infection.
Although limited clinical information is available concerning drug-drug
interactions involving psychotropic and antiretroviral medications,
effective psychotropic medication management in the setting of HIV
requires attention to possible interactions.
Potential drug-drug interactions in the setting of antiretroviral
therapy include the effects of antiretroviral agents on psychotropic
medications and vice versa. Protease inhibitors and nonnucleoside
reverse transcriptase inhibitors are metabolized by the cytochrome
P450 system and may inhibit or induce multiple isoenzymes. For example,
the protease inhibitor ritonavir inhibits the cytochrome P450 isoenzymes
3A, 2D6, and 2C9/19; thus, most psychotropic medications
may be affected when concomitantly used with ritonavir.
Other protease inhibitors tend to only inhibit the cytochrome P450 isoenzyme
3A, thus limiting possible drug-drug interactions to psychotropic
medications metabolized via this pathway (e.g., some benzodiazepines,
citalopram, and nefazodone).
The nonnucleoside reverse transcriptase inhibitors also require
careful attention. For example, nevirapine and efavirenz are metabolized
via the cytochrome P450 isoenzymes 3A and 2B6 and induce cytochrome
P450 activity, which could result in decreased psychotropic concentrations
at standard doses (278). Delavirdine, another nonnucleoside
reverse transcriptase inhibitor, inhibits the cytochrome
P450 isoenzyme 3A and reduces hepatic clearance of psychotropic
agents primarily metabolized by this pathway (279). The protease
inhibitors and nonnucleoside reverse transcriptase inhibitors are
among the most problematic of the antiretrovirals when coadministered
with psychotropic medication. Table 15 indicates the relative rank
order of inhibition potency of the currently available protease
Protease Inhibitor
Cytochrome P450 Isoenzyme
For combination antiretroviral therapy that includes protease
inhibitors and nonnucleoside reverse transcriptase inhibitors,
an overarching concern in terms of coadministration with
psychotropic agents is not only the possibility of plasma levels
of psychotropic medications outside the targeted therapeutic concentration
range but also the possible reduction of antiretroviral levels to
the point of risking their effectiveness. While most interactions inhibit the
cytochrome P450 system, some clinically important drug interactions
also induce this system with medications
used to treat co-occurring medical conditions in HIV disease (e.g., glucocorticoids,
rifampin, phenytoin). Table 16 provides an overview of psychotropic
agents and HIV therapies, routes of metabolic inhibition and induction,
and potential clinical concerns.
P450 Isoenzyme
Medications That
Inhibit Isoenzyme
Psychotropic Medications Primarily Metabolized
by Isoenzyme
Clinical Implications of
Isoenzyme Inhibition
Medications That
Induce Isoenzyme
Clinical Implications of
Isoenzyme Induction
Protease inhibitors (especially ritonavir)
Increased plasma levels and increased
side effects;
for benzodiazepines,
sedation and decreased respiratory drive
Decreased plasma
levels of psychotropic medications and
decreased effectiveness
Protease inhibitors (especially ritonavir
and nelfinavir)
Increased plasma levels and increased
side effects; for tricyclic antidepressants, potential increased risk
for cardiac conduction delay
typical and
Although the aforementioned risks for drug-drug interactions
may seem substantial, to date, clinical data have not revealed severe
side effects among most patients receiving antiretrovirals in conjunction
with psychotropic medications (50).
A few reports have documented the inhibitory effects of
protease inhibitors. For example, when coadministered with ritonavir,
desipramine levels have been shown to increase 145% in
vitro (280) and to increase to some extent when coadministered with
other protease inhibitors (281). In a clinical setting, coadministration
of saquinavir and midazolam has caused prolonged sedation (282).
These in vitro and in vivo data should lead to careful monitoring
for potentially problematic or dangerous side effects in patients
taking antiretrovirals.
Drugs of abuse can also cause drug-drug interactions. MDMA,
an amphetamine derivative also known as "ecstasy" that
is primarily metabolized via the cytochrome P450 isoenzyme 2D6,
reportedly led to a lethal overdose when taken by a patient being
treated with ritonavir (283). Other drugs of abuse, particularly
those metabolized via the cytochrome P450 isoenzymes 2D6
or 3A (e.g., amphetamines, ketamine, heroin, cocaine, and -hydroxybutyrate)
may lead to toxic events when taken by patients being treated with
protease inhibitors.
Although some drug-drug interactions may be only theoretical,
it is prudent for clinicians to explain these concerns during the
informed consent process of psychotropic prescribing. Because of
the extent of comorbid substance abuse among some HIV patients,
a general warning of the possible interactions of combining antiretroviral
agents, psychotropic medications, and recreational drugs is often
indicated. Web sites are available to clinicians and patients that
address antiretroviral drug interactions and may be useful
educational and reference tools (http://www.aegis.com; http://www.drug-interactions.com;
and http://www.dml.georgetown.edu/depts/pharmacology/davetab.html).
Psychiatrists should remember that HIV patients who have been
clinically stable on regimens of maintenance psychotropic medications
and who later initiate combination antiretroviral therapies may
require adjustments or changes in their psychotropic regimen. The
rational choice of psychotropic medications must also include critical
considerations of adherence. Generally, it is important to minimize
the number of drug doses and to tie dosing to times of the day with
natural cues (e.g., meals, work schedule, bedtime). Outlined here
are unique factors to consider in administering specific psychotropic
agents to HIV patients, particularly those patients simultaneously
receiving antiretroviral therapies.
The prevalence of mood disorders in HIV patients is higher
than general population rates; evidence from effectiveness studies
and clinical trials indicates that antidepressants are generally
well tolerated by HIV patients, even those with symptomatic HIV
infection or AIDS (284–290). Thus, antidepressants are
commonly prescribed to HIV patients for the treatment of depression
as well as for other HIV-related conditions, such as chronic pain
(e.g., peripheral neuropathy) (291). However, clinicians must be
cautioned that two factors may limit the generalizability of some
antidepressant studies. First, many studies of antidepressants in
HIV patients were conducted before the availability of combination
antiretroviral therapy and thus did not take into account possible
pharmacokinetic complications (292). Second, a minority of published
psychopharmacology studies has included patients with advanced stages
of HIV infection or AIDS. There is, to date, no evidence to suggest adverse
effects of antidepressants on the immune system (293).
Several studies have indicated that tricyclic antidepressants
are less well tolerated than SSRIs (287, 294), leading some to recommend
SSRIs over tricyclic antidepressants (277). One study
found that despite efficacy for treating depression, fluvoxamine
was poorly tolerated by HIV patients (295). Because similar metabolic
pathways, particularly the cytochrome P450 isoenzyme 2D6, are utilized by
SSRIs and ritonavir, the psychiatrist should maintain communication
with other clinicians treating the patient. Although SSRIs are generally
well tolerated across a broad range of blood levels, the untoward
outcome of serotonin syndrome may be possible in some cases in which
the cytochrome P450 isoenzyme 2D6 is inhibited (296). While the
SSRIs themselves inhibit this isoenzyme, the potency of their inhibition
is less than that of ritonavir. However, the potential impact of
SSRI-related inhibition of the cytochrome P450 isoenzyme 2D6 should
be remembered when coadministering SSRIs with other agents
that are substrates of the cytochrome P450 2D6 isoenzyme.
While tricyclic antidepressants are metabolized
by other cytochromes, they rely principally on the cytochrome P450
isoenzyme 2D6 for clearance. Therefore if tricyclic antidepressants
are coadministered with ritonavir, monitoring of ECG results and
tricyclic antidepressant plasma levels is recommended because of
the possibility of increased tricyclic antidepressant plasma levels
from cytochrome P450 inhibition and associated tricyclic antidepressant
side effects (e.g., delayed cardiac conduction, anticholinergic
effects, orthostasis).
Nefazodone and the protease inhibitors are both potent inhibitors
of the cytochrome P450 isoenzyme 3A, and their combination may be
problematic. Nefazodone administration may theoretically decrease
the metabolism of some protease inhibitors, leading to increased
protease inhibitor plasma levels and increased side effects. However,
one study that examined the efficacy of nefazodone in HIV patients
found that only one of 15 patients had a clinically significant
drug interaction that was related to coadministration with ritonavir
(288). Of general concern is the coadministration of nefazodone
or protease inhibitors with the antipsychotic pimozide, which can
cause cardiac arrhythmias at increased plasma levels (296). Other
potentially dangerous interactions with inhibitors of the cytochrome
P450 isoenzyme 3A include the coadministration of most benzodiazepines (respiratory
depression), clozapine (seizures), ergot alkaloids (sustained systemic
vasoconstriction), and sildenafil (priapism).
Venlafaxine has been reported to decrease the concentration
of indinavir significantly even though a lack of such interaction
was predicted based on each drug's pharmacokinetic parameters.
At this time, venlafaxine should be avoided in those patients receiving
indinavir, since decreases in concentration of protease inhibitors
can affect treatment efficacy and increase the chances for viral resistance
to develop (297).
Previously it was thought that bupropion was eliminated via
the cytochrome P450 isoenzyme 2D6. However, recent data have shown
that it is actually cleared via the 2B6 isoenzyme. Therefore, bupropion
has been removed from the list of drugs contraindicated with ritonavir,
and this is reflected in the revised product monograph.
No adverse events have been reported with the agents citalopram
and mirtazapine. Citalopram has minimal inhibitory actions
on the cytochrome system and may be particularly useful for patients taking
multiple medications where drug-drug interactions are an ongoing
concern. Mirtazapine, because of its sedating profile, may be particularly
useful for depressed patients with insomnia. It may also be helpful
for patients with poor appetite because of its tendency to increase
appetite and also helpful for patients who may be prone to sexual
dysfunction with other antidepressant agents.
Generally, the use of antipsychotic medication among patients
with advanced HIV infection is associated with an increased incidence
of extrapyramidal side effects. High-potency standard neuroleptics
(haloperidol is the most commonly used in published reports) can
be associated with severe dystonia, rigidity, akathisia, and parkinsonism
(31, 298–301). Low-potency standard neuroleptics can also
result in severe extrapyramidal side effects but overall appear
to be less problematic than high-potency neuroleptics (302–305).
A study that contrasts with the perspective that standard
neuroleptics are associated with severe extrapyramidal side effects
in advanced HIV infection was conducted in hospitalized patients
with AIDS who were randomly assigned pharmacologic treatment for
delirium; 13 received chlorpromazine, and 11 received haloperidol
(46). The study stated that "no clinically significant
medication-related side effects were noted." However,
patients were treated with very low doses of neuroleptic (i.e.,
average maintenance doses were 36 mg/day for chlorpromazine
and 1.4 mg/day for haloperidol). The study is consistent
with the rest of the literature in stressing the importance of treating
patients with advanced HIV infection with the lowest possible effective
dose when using a typical neuroleptic.
Neuroleptic malignant syndrome has been noted with standard
neuroleptics in five reports. In one case, neuroleptic malignant
syndrome occurred within 24 hours; in the four other cases, neuroleptic malignant
syndrome occurred within days of initiating treatment (300, 306–309).
All patients recovered with usual management. Onset of tardive dyskinesia
has been reported within a period as short as 6 weeks or within
months (31, 310, 311). Confusion has also been reported with standard neuroleptics
Most patients with extrapyramidal side effects respond to
typical treatments, but one case report of a patient with parkinsonian
side effects noted a slow response (299). Another patient had no response
to multiple antiparkinsonian agents (313). Scurlock et al. (298)
reported an AIDS patient who developed a grand mal seizure while
taking chlorpromazine, and Jones et al. (314) reported a grand mal
seizure in one man with symptomatic HIV infection who was taking
amitriptyline and chlorpromazine.
Atypical antipsychotic agents appear to be better tolerated
with fewer serious side effects, as evidenced by two case series
of 30 combined patients who received risperidone (310, 315), one
report of four patients who received remoxipride (298), and another
of four patients who received molindone (312). Some of these patients
had previously experienced severe side effects while taking typical neuroleptics.
All were able to tolerate the atypical agents, and most but not
all patients had a good therapeutic response. The most common side
effects seen with risperidone were drowsiness and drooling
(315). Extensive clinical experience suggests that olanzapine is
also well tolerated for the treatment of psychosis, delirium, and
behavioral disturbances among HIV patients.
It is of interest that movement disorders, including dystonia
and parkinsonism, have been reported in advanced HIV infection without
exposure to neuroleptics (316, 317). In the one case report of irreversible
extrapyramidal side effects in a man with HIV-associated dementia
following exposure to standard neuroleptics, an autopsy revealed
numerous microscopic changes, including neuronal loss in the basal
ganglia (313). It may be that damage to the basal ganglia is a factor
that increases the susceptibility of HIV patients to extrapyramidal
side effects after neuroleptic administration (318). A similar pattern
of extrapyramidal side effect susceptibility in concert with neuronal
damage has been described in the elderly (311, 319).
For all antipsychotic agents, the possibility of drug-drug
interactions must be considered for those patients also taking antiretroviral
medication. Antipsychotic dosage adjustments may be required to minimize
side effects such as extrapyramidal side effects. Because of the
rare dose-related side effect of agranulocytosis among patients
taking clozapine, this particular agent should be monitored closely if
given to any HIV patient (320). Likewise, clinicians should monitor
for risk of seizures if clozapine is administered with
ritonavir, since ritonavir inhibits the cytochrome P450 isoenzyme
2D6, clozapine's primary metabolic pathway. Pimozide should
also be used cautiously in combination with any inhibitor of the
cytochrome P450 isoenzyme 3A because of risk of fatal
arrhythmias at elevated doses. Depot antipsychotic medication should
be avoided in advanced HIV disease.
Psychostimulants, such as methylphenidate and dextroamphetamine,
are frequently used in HIV patients with neurocognitive impairment,
fatigue, and, to a lesser extent, in some patients with depression
(321, 322). These drugs are generally safe and well tolerated with
no drug-drug interactions reported to date among HIV patients. The
possibility of dopamine agonism inducing psychosis should be considered
in vulnerable patients, such as those with a history of HIV-related
CNS complications or a history of psychosis. Psychostimulants should
be avoided or used judiciously among patients with a past or current
history of amphetamine abuse.
Use of valproate in patients with bipolar disorder is not
uncommon, particularly among HIV patients who develop mania secondary
to HIV-related complications or psychoactive substance use. Concerns
have been raised about the potential for valproate to possibly accelerate
disease progression in HIV-positive patients. This concern is based
on the fact that valproate has been shown in vitro to lower glutathione
levels, which leads to activation of HIV replication (323). However,
a retrospective review by Maggi and Halman (324) of 11 patients
with HIV infection who were also treated with valproate found no
evidence of increased viral load in those receiving adequate antiretroviral
The metabolic pathways of valproate are not fully delineated,
but this agent has been associated with hepatotoxicity. There is
a case report of valproic acid–induced hepatotoxicity when
valproate was used together with ritonavir and nevirapine (325).
Valproate inhibits glucuronyl transferase. Zidovudine uses glucuronyl
transferase as its primary pathway of metabolic clearance. Therefore, increased
plasma levels of zidovudine and associated side effects could result
when the two agents are combined.
Generally, divalproex sodium is better tolerated than valproic
acid, since it produces fewer gastrointestinal side effects and
can be dosed less frequently (two or three times a day rather than four),
particularly among HIV patients who may have preexisting gastrointestinal
illness. Increased side effects may be caused by increased concentrations
of free valproate in HIV patients because of factors such as the
reduction of plasma protein levels, the increased percentage of
free drug due to chronic illness, or drug-drug interactions that
may decrease protein binding of valproate (326).
Lithium is commonly used in HIV patients with primary bipolar
disorder. Because it does not require hepatic metabolism, it is
a rational choice for many patients taking antiretroviral agents
who require extensive hepatic metabolism. Lithium should be used
with great caution in patients who develop HIV-related nephropathy,
a generally irreversible complication that can lead to decreased lithium
clearance and possible lithium toxicity. When given at doses necessary
to maintain serum lithium concentrations between 0.5 and 1.5 meq/liter,
lithium has been associated with signs of toxicity in some HIV patients,
even among patients without renal disease (327). Thus, clinical experience
suggests that lithium is best avoided in patients with probable
AIDS mania or advanced HIV disease due to risk of toxicity.
Although not absolutely contraindicated, carbamazepine is
used less commonly in HIV patients because of its potential to cause
bone marrow complications (e.g., leukopenia or aplastic anemia). This
risk should be avoided in immunocompromised patients. Carbamazepine,
like other anticonvulsants, phenobarbital, and phenytoin, is known
to induce activity of the cytochrome P450 isoenzyme 3A. This induction
can accelerate antiretroviral drug metabolism and possibly cause decreased
plasma levels and diminished efficacy. It is recommended that carbamazepine
concentrations be closely monitored.
Lamotrigine, gabapentin, and topiramate are newer anticonvulsants
that have recently been used off-label to treat selected populations
of patients with bipolar disorder, typically those with rapid cycling,
mixed mood states, or bipolar depression. While no data currently
support their use for mood disorders in HIV patients, gabapentin
may offer some advantages over other anticonvulsants because it
is neither protein bound nor metabolized by the liver. Gabapentin
is thus less likely than other anticonvulsants to lead to drug-drug
interactions. Gabapentin has been successfully used in HIV patients
to treat peripheral neuropathy, which can be both a complication
of HIV disease and a side effect of some antiretroviral agents.
Buspirone is commonly used and generally well tolerated in
HIV patients as a treatment for generalized anxiety disorder (328).
There are no reports of HIV-related drug-drug interactions with buspirone.
However, one case report describes induction of manic psychosis
following a single dose of buspirone in a patient with asymptomatic
HIV illness (329).
Benzodiazepines are commonly used in HIV patients and are
best used for short periods to minimize the risk of tolerance or
addiction and to maximize effectiveness. This class of drugs is generally
best avoided in patients with alcoholism and those with a history
of substance abuse. Benzodiazepines are metabolized primarily by
the cytochrome P450 isoenzyme 3A; however, oxazepam, lorazepam,
and temazepam are metabolized by direct conjugation via glucuronyl
transferase, resulting in shorter elimination half-lives and less
likelihood of metabolite accumulation and associated side effects.
When some benzodiazepines are coadministered with inhibitors
of the cytochrome P450 isoenzyme 3A (such as protease inhibitors),
one would expect a decrease in benzodiazepine clearance with increased
sedation, potentially resulting in respiratory depression. Even
saquinavir's relatively low-potency inhibition of the cytochrome
P450 isoenzyme 3A has been shown to prolong the sedative effect
of midazolam (282). Although one study that examined the
chronic effect of ritonavir administration on alprazolam metabolism
reported a 10%–15% decrease in expected
alprazolam levels (330), a more recent study found that short-term,
low-dose ritonavir administration significantly impaired alprazolam
clearance (331). These studies call attention to the need for judicious
use of alprazolam in combination with ritonavir.
An additional consideration when using benzodiazepines that
are metabolized by glucuronidation (e.g., oxazepam, lorazepam, temazepam)
involves ritonavir's inductive effect on glucuronyl transferase
activity (332). The concentration of glucuronyl transferase substrates
may be decreased when these agents are coadministered with ritonavir.
Therefore in some cases, patients taking one of these three benzodiazepines
may require higher doses for symptom control. Benzodiazepine-dependent patients
may also require higher doses to avoid the onset of withdrawal (296).
Some patients with wasting syndrome can be helped by medications
that serve as appetite stimulants to combat loss of appetite and
associated weight loss. Four agents currently have been approved
by the Food and Drug Administration (FDA). Two of these agents,
dronabinol and oxandrolone, are Schedule II controlled substances.
Because these agents have unique psychiatric side effect profiles,
they should be monitored closely among patients who receive psychiatric
Dronabinol is a cannabinoid indicated for HIV-associated anorexia
and nausea. It is a major active metabolite in marijuana and, like
marijuana, has complex effects on the CNS, including sympathomimetic
activity. Oxandrolone is an anabolic steroid synthetically derived
from testosterone that is used for weight gain and promotion of
lean body mass (333–335). Its side effect profile is similar
to that of other anabolic steroids, including mood effects. Another
agent, megestrol acetate, is a synthetic derivative of progesterone
that increases fat rather than muscle gain. It also lowers testosterone
and may produce side effects (e.g., mood disturbances) similar to
those associated with glucocorticoids. Somatotropin is an injectable
form of recombinant human growth hormone indicated for the treatment of
AIDS wasting and cachexia (336–340). It is an anabolic
and anticatabolic treatment that combats the loss of lean body mass
and is generally well tolerated by patients. The effects of somatotropin are
often lost when it is discontinued.
These medications can be extremely beneficial for patients
with significant anorexia, weight loss, and nausea. However,
because they are usually used in more advanced stages of HIV disease,
when patients are more medically frail and receiving multiple other
medications, psychiatrists should actively monitor response, side
effects, and drug interactions. Limited data do not indicate a high incidence
of psychiatric side effects.
Thalidomide, a potent teratogen once marketed as a sedative
and morning sickness agent in the 1950s and 1960s, is currently
available on a restricted basis for HIV patients for the
treatment of wasting syndrome (341, 342). The agent is FDA-approved as
an immunomodulatory drug for the treatment of severe HIV-related
oral ulcers. Prescribing physicians must register under a special restricted
distribution program with the FDA. Primary psychiatric side effects
include CNS depression; few data are available concerning drug-drug
interactions, although thalidomide does not appear to be metabolized
by the liver to any large extent.
A number of clinical trials have found testosterone to be
effective in the treatment of a number of HIV-related symptoms (e.g.,
fatigue, wasting, impaired sexual functioning, and mild depression) often
associated with more advanced HIV disease (126, 343, 344). Although
typically used to treat hypogonadism in the general population,
clinical response to testosterone in HIV patients is not correlated
with serum testosterone levels at baseline. HIV-infected
men with normal levels of testosterone respond as well as those
with lower than normal levels (126). The most common psychiatric
side effects of testosterone are changes in mood and irritability.
Many HIV patients are treated with opiate analgesics for both
acute pain syndromes, such as that associated with Candida esophagitis,
as well as chronic pain conditions (e.g., neuropathic and myopathic
pain syndromes). Chronic pain is also common in advanced HIV disease,
particularly among cachectic patients with wasting syndrome. Because
opioids are metabolized primarily via the cytochrome P450 isoenzymes 2D6
and 3A, they should be used cautiously in conjunction with antiretroviral
agents that are likely to increase their plasma levels.
Some opioids, such as codeine and hydrocodone (as well as
the nonopiate tramadol), must be converted into active
metabolites to produce analgesic effects. This conversion can be
blocked by cytochrome P450 inhibitors, which results in reduced
pain control in addition to adverse reactions from the buildup of
unmetabolized drug (345). Oxycodone and morphine, which are primarily glucuronyl
transferase substrates, are alternatives for pain control. However,
in the presence of a glucuronyl transferase inducer such as ritonavir,
their analgesic effect can be diminished as well (296, 332). As
HIV disease progresses, the provision of safe, effective pain control
requires clear understanding of the above factors.
There is limited information available on the extent and clinical
implications of drug interactions in HIV-positive patients with
comorbid substance use disorders. However, several studies have
been published. Methadone has been shown to significantly increase
zidovudine levels, but zidovudine has not been shown to affect methadone
levels (346–348). Interim results from a study of the interaction
of zidovudine with LAAM, buprenorphine, or naltrexone indicate that
LAAM does not affect zidovudine levels, whereas buprenorphine may
decrease levels nonsignificantly (349). Another report indicates
that abacavir, a newer nucleoside analogue reverse transcriptase
inhibitor, increases methadone clearance, although the proposed
mechanism remains unclear (350). Preclinical studies of the coadministration
of protease inhibitors and methadone revealed that ritonavir causes
a twofold increase in the area under the curve for methadone level
and that indinavir causes a 30% increase, compared to no
increase with saquinavir (351). One case report has indicated that
nelfinavir may induce cytochrome P450 enzymes leading to decreased
methadone levels (352). Nevirapine and efavirenz induce cytochrome
P450 enzymes important to methadone metabolism and are reported to
precipitate opiate withdrawal symptoms in methadone maintenance
patients (278, 353). The consequences of undetected drug
interactions among opioid-dependent patients are complicated and include
nonadherence with treatment regimens, the potential development
of resistant HIV strains, increased illicit drug abuse, drug toxicity,
and loss of efficacy. In administering methadone to HIV patients
taking protease inhibitors or nonnucleoside reverse transcriptase
inhibitors, clinicians should adjust doses to compensate for cytochrome
P450 enzyme effects.
There is no clinical information regarding the use of disulfiram
in patients with HIV infection. Psychiatrists should therefore follow
general guidelines for the use of disulfiram
cautiously. Naltrexone, an opioid antagonist, is indicated in the
treatment of alcohol dependence and for the blockage of the effects
of exogenously administered opioids. Because naltrexone can cause
hepatocellular damage when given in excessive doses, it should be
used cautiously in patients with liver disease. It should
also be noted that naltrexone's opioid antagonism might
block the clinical effects of some commonly used medications in
HIV patients that contain opioids (e.g., antidiarrheal
medications, cough and cold preparations).
Patients with HIV infection may use a wide range of alternative/complementary
agents for preventive and symptomatic treatment of HIV-related complications.
Of particular interest to psychiatrists are those agents used to
treat psychiatric symptoms. For example, patients may take Hypericum
perforatum (St. John's wort) or the nutritional
supplement S-adenosylmethionine
(or SAM-e) to treat depression, kava kava for anxiety, melatonin
or valerian root for insomnia, and ginkgo biloba for memory problems.
One published report found that St. John's wort, which
contains an inducer of the cytochrome P450 isoenzyme 3A, dramatically
lowered levels of indinavir (and presumably other substrates of
the cytochrome P450 isoenzyme 3A) (354). The FDA thus
issued a public health advisory that concomitant use of St. John's
wort with protease inhibitors and nonnucleoside reverse transcriptase
inhibitors is not recommended. There are no data regarding other
alternative/complementary agents at this time.
Since the beginning of the AIDS epidemic, psychosocial support
has emerged as a cornerstone of the comprehensive treatment for
many persons infected and affected by HIV/AIDS. For many
HIV patients, psychotherapy and psychosocial interventions have
been invaluable in the search for meaning during the course of living
with HIV (355). Psychotherapy can be an important intervention to
address conditions that may interfere with a patient's
acceptance of HIV illness or their ability to work cooperatively
with their health care team. With the advent of new antiretroviral
treatments, new psychotherapy themes have emerged, including changes
in role definitions and life trajectory as well as treatment adherence
challenges (356–358).
For patients who are socially disenfranchised, psychosocial
treatments may consist of basic services that assist them in gaining
access to food, shelter, transportation, and child careessential elements
of a care plan that diminish health care delivery barriers and promote
mental health care utilization.
Generally, psychosocial treatments are those treatments, often
offered in the community, that provide direct assistance along such
parameters as social adjustment, social support, coping, and overall
adjustment to HIV infection. Psychosocial interventions often occur
in group formats, such as informal support groups, although more
formal groups may tailor their membership (i.e., women, men, mothers,
caregivers) or their mission (HIV risk reduction, treatment adherence)
(359, 360). Other formats include peer counseling, a supportive
intervention typically offered by HIV-positive consumers based in
community AIDS service organizations.
Other psychosocial treatments have been developed that incorporate
a service model (e.g., psychosocial rehabilitation programs for
persons with HIV/AIDS, day treatment programs for HIV-positive
persons with neurocognitive impairment) or a service theme (e.g.,
permanency planning for parents with advanced AIDS, HIV prevention,
case management, disclosure of HIV status) (67, 79, 355, 361).
Researchers have described a wide range of psychological and
psychosocial sequelae from HIV/AIDS (251). In their review
of empirical findings, Kalichman and Sikkema (362) showed that psychological
complications include distress, anger, guilt, bereavement, and the
full spectrum of psychiatric disorders. Syndromes such as depression
may appear, subside, and recur during the course of living with
HIV/AIDS. Moreover, certain psychosocial conditions, such
as increased social support and fewer incidents of HIV-related discrimination,
have been shown to predict greater life satisfaction among HIV patients
Psychosocial treatment of HIV-related complications will often
involve referral of patients to community AIDS service organizations
that specialize in the provision of psychosocial support. While
many of the treatment issues are also themes that will emerge in
psychotherapy (i.e., stigma, coping strategies, or disclosure of
HIV status), support groups and other interventions provide a model
for structuring social support over the course of living with HIV
infection (362). Psychosocial services may take on added importance
for patients living in rural regions, in which more community HIV-related
stigma has been documented (143).
Psychosocial interventions have been shown to enhance adaptive
coping strategies, social support, perceived sense of meaning and
purpose, and self-esteem and also have been shown to lower anxiety and
HIV risk behaviors among HIV-positive adults (359, 363–365).
Because of the spectrum of social, psychological, and neuropsychiatric
consequences of HIV/AIDS, psychiatric treatment should
consider the relevance for a given individual of a wide variety
of potential psychosocial interventions, spanning the spectrum from
individual to family or group psychotherapy as well as psychodynamic/psychoanalytic,
interpersonal, behavioral, or supportive approaches.
Psychiatrists caring for HIV-infected patients can be faced
with complex legal and ethical issues, some of which are unique
to HIV infection. The AIDS Litigation Project conducted a national
review of cases that involved individuals with HIV/AIDS
in the federal and state courts in the United States between 1991
and 1997. The review identified important subsets of litigation,
which included issues of "testing and reporting; privacy,
the duty to warn, and the right to know; physician standards of care
in prevention and treatment; and discrimination and access to health
care" (366).
Most U.S. states have legal requirements surrounding HIV testing
that require written informed consent and a minimum amount of pre-
and posttest counselingboth to those who test positive
and to those who test negative. Furthermore, many states are required
to report positive HIV test results to public health agencies. Some
states mandate that the report include the name of the individual
who tested HIV positive. All states have mandatory name reporting
when a patient is diagnosed with an AIDS-defining condition.
For those infected with HIV, confidentiality of HIV status
is often paramount, especially for patients who are asymptomatic
or who are concerned about possible discrimination by
their employers or by insurance companies. Psychiatrists are typically
attuned to confidentiality issues and regard patient-doctor confidentiality
as fundamental to effective treatment. Yet, there are limits to
confidentiality, such as when there is potential for others to be
harmed, and these limitations should be discussed with patients
when treatment is initiated.
For persons infected with HIV, particularly those recently
diagnosed, their recent sexual partners and/or those with
whom they share injection equipment should be informed of their
potential exposure to HIV. These partners can benefit from HIV counseling
and testing and knowing their HIV infection status. Many health
departments offer services known either as "partner notification" or prevention
counseling and referral services (367–369).
Another important issue involves the dangerousness of HIV
patients. A patient with HIV infection is not a danger to others
in the absence of imminent threats to harm others. In general, there
are no legal requirements for physicians to inform partners of HIV-infected
patients of their HIV status, especially if the patient agrees to
notify their partner or if they are clearly practicing "safer
sex." However, because HIV-infected patients are able to
transmit the virus and potentially put others in danger of infection,
psychiatrists who care for HIV patients have an ethical requirement
to counsel their patients about modes of HIV transmission and promote
safer behavior, such as the consistent use of condoms and/or
the use of clean needles. Psychiatrists can offer to assist patients
in notifying individuals at risk or help refer a patient to public
health officials for partner notification, if necessary.
On the other hand, if a patient has not disclosed their HIV-positive
status to a partner and continues high-risk behavior, psychiatrists
may have a duty to warn identifiable sexual partners or other at-risk individuals.
APA policy reads that, "If a patient refuses to change
behavior that places others at risk for HIV infection or to inform
individuals at ongoing risk, or if the psychiatrist has good reason
to believe that the patient has failed to or is unable to cease
such behaviors or to inform those at risk, it is ethically permissible
for the psychiatrist to notify identifiable individuals at risk
or to arrange for public health authorities to do so" (370).
Psychiatrists need to be mindful that while it may be ethically permissible
to notify, it may not be legally permissible,
and therefore psychiatrists should obtain legal advice before breaching
For patients who are impulsive or psychotic, protective measures
such as voluntary or involuntary psychiatric hospitalization are
options for treatment of psychiatric disorders and protection of
others. For antisocial individuals, hospitalization should not be
used merely as a means of social control.
During the course of HIV illness, and especially after the
onset of AIDS, patients may experience cognitive impairment or symptoms
of dementia. Such disturbances may affect a patient's ability
to give informed consent to accept or refuse treatment. When psychiatrists
are asked to conduct competency evaluations for patients with HIV/AIDS,
a comprehensive mental status examination that includes an evaluation
of cognition is critical, followedif indicatedby
formal neuropsychological testing and assessment of specific treatment
decision-making capacity.
The opposite of a patient's refusal of treatment
is the refusal on the part of physicians to provide HIV treatment
to psychiatric patients. Because antiretroviral therapies involve
complex medication regimens and adherence to treatment is critical,
physicians may be biased against prescribing these treatments to
patients with a comorbid mental illness such as a substance use
disorder. While refusal of treatment due to poor adherence is appropriate,
refusal of treatment solely on the grounds of a mental illness is
not. When the psychiatrist is a consultant who does not intervene
directly in the care of the patient, he or she will need to work
with the primary clinician to help ensure that appropriate psychiatric
treatment is received (371).
Potent antiretroviral treatment has given hope to patients
infected with HIV yet simultaneously has increased the complexities
of managing HIV illness (372). For instance, the combination of
three or more medications used in most antiretroviral treatment
regimens makes adherence difficult. In addition, some medications
must be taken with food, others without food; dosing is usually
twice a day but sometimes can be more frequent. Side effects can
be significant, requiring discontinuation or the initiation of a
new combination of medications. Because antiretroviral treatment
should begin as an aggressive broad attack on HIV replication, doses
of the drugs are generally not titrated upward but rather are initiated
at the full dose. Thus, patients may experience many initiation
side effects.
Adherence to antiretroviral therapy regimens is critical,
as evidenced by a study that measured adherence by using a microelectronic
monitoring system (95). The authors found that 95% adherence to
treatment was associated with complete viral suppression but that
failure rates increased sharply with less than 95% adherence.
Researchers have documented that patients who receive potent antiretroviral
treatment but who are not enrolled in clinical trials show viral
suppression rates one-half those of study patients, which suggests
the real-world difficulty of maintaining strict adherence (373).
Adherence to any kind of medical treatment is a well-established
problem. Overall adherence rates vary from 20% to 80% and
average 50% (374). Psychiatrists should make every effort
to treat and control psychiatric disorders that affect a patient's
ability to maintain close adherence to an HIV treatment regimen.
Each year, about 7% of patients with AIDS develop HIV-associated
dementia (375). This condition can interfere with ability to follow
and understand treatment regimens. In addition, researchers have
found that depression can be a cause of nonadherence and that treatment of
depression might thus improve medical outcomes (96). Strategies
that have proven useful in improving adherence for both psychotropic
and antiretroviral medication have been reported and are summarized
below (376).
How a health care system is structured will strongly influence
whether clinicians and patients can collaborate and enhance adherence.
One important element is a respectful and culturally sensitive environment.
The availability and continuity of clinicians over time with 24-hour/day
phone coverage to handle crises that might disrupt a regimen (severe
side effects, loss of medication), as well as clinician caseloads
that permit time for adequate discussion with patients, all promote
adherence. Hospitals do not always dispense medications on the 8-
or 12-hour schedules required for antiretroviral dosing. Last, social
service mechanisms such as case management for handling financial
and logistical barriers to obtaining and following the regimens
provide crucial support.
When initiating antiretroviral treatment, it is essential
for the physician to prepare the patient. Because the best chance
at viral suppression occurs with the first regimen, it makes sense
to wait until the patient is ready. For a psychiatrist, it is important
to treat or recommend treatment for comorbid alcohol/substance
use disorders, depression, psychotic illnesses, or personality disorders that
are likely to interfere with adherence (377). At the same time,
if the patient is motivated to begin antiretroviral treatment, this
can be a good opportunity to introduce psychiatric or substance
use treatment if indicated.
Multiple approaches to enhancing adherence are often needed
(Table 17). For longer-term adherence, individual medication management,
in which a staff member provides assessment and problem-solving
support, may improve adherence (378).
Prepare patients
Discuss use of medications before prescribing
Outline pros and cons of therapy
Acknowledge commitment required, consequences
of noncompliance, and
benefits of therapy
Provide written instructions
Inform patients of expectations, including
side effects
Provide information on who patients
should call if significant side effects occur
Schedule a follow-up appointment soon
after initiating therapy
Review importance of therapy
Inform patients that they must continue
to take all medications
Review the effects of stopping one
Outline procedure for obtaining refills
Recognize patient lifestyle and preferences
Twice-daily dosing benefits may outweigh
initial side effects; ritonavir may be preferred
Consider whether patients prefer tolerability
over convenience; nelfinavir or indinavir may be preferred
Discuss midday dosing
Recommend medication timers or calendar
Help patients plan for away-from-home
Simplify regimens
If possible, prioritize or eliminate
medications when patients are overwhelmed
Look for and address nonadherence
Consider regimens that minimize cross-resistance
Use regimens that leave options for
future effective antiretroviral therapy
Inquire about adherence
Inquire about medication-taking behavior
at each visit
Anticipate relapses in adherence, even
after long-term use of medication
There are numerous psychiatric difficulties that can occur
in the context of HIV infection, yet studies of the treatment of
HIV-related psychiatric disorders are limited. This section summarizes the
existing scientific literature on the treatment of specific psychiatric
disorders for patients with concurrent HIV/AIDS.
Most research studies on the treatment of cognitive disorders
associated with HIV infection have focused on HIV-associated dementia.
Fewer studies have looked at the benefits of intervention at earlier
stages of cognitive decline despite the possibilities for treating
disorders, such as minor cognitive motor disorder, that involve
neuronal cell dysfunction rather than cell death. Treatment of neuropsychological
impairment without clinical disorder has been studied to some extent,
and protection against neuropsychological impairment has been studied
Pharmacologic treatment strategies for cognitive disorders
can be divided into four types: 1) antiretroviral therapies, 2)
therapies aimed at immunological measures or inflammatory mediators, 3)
therapies aimed at bolstering the response of the brain
to the onslaught of the infection (e.g., neurotransmitter
manipulation), and 4) nutritional therapies. Most controlled
studies have investigated the efficacy of antiretroviral
therapies, and while these studies have advanced our knowledge about
interventions for cognitive disorders, several key factors must
be kept in mind. First is the fact that most published studies to
date report on the treatment strategy of administering a single antiretroviral
agent. Their findings are therefore difficult to interpret in light
of the multidrug regimens that are now the standard of care in developed
countries. Second, the reports vary widely with regard to the study
population, since some studies enrolled subjects on the basis of
established criteria for HIV-associated dementia or minor
cognitive motor disorder but other studies enrolled cognitively
impaired subjects without specifying whether they also met criteria
for a clinical disorder. Third, the range of HIV clinical severity
also varied widely in study subjects.
Whether antiretroviral agents penetrate the blood-brain barrier
sufficiently to adequately suppress viral replication is a key issue
that requires further study (379, 380). We know that near-perfect adherence
to antiretroviral therapy is required to maintain plasma viral load
at undetectable levels. Even in the best-case scenario, if decreased
plasma viral load is achieved and levels of antiretroviral agents
in CSF or brain tissue are optimized, it is not yet known whether
complete suppression of replication in the CNS can be achieved (381).
Another theoretical concern is that if antiretroviral resistance
develops in the CNS, it is possible that resistant HIV could then
reseed the peripheral circulation. This mechanism could potentially
lead to increased prevalence of neurocognitive disorders as well
as systemic progression of HIV disease.
Two randomized, placebo-controlled clinical trials have provided
evidence for the effectiveness of zidovudine in reducing neuropsychological
impairment for patients with HIV infection. Sidtis and colleagues
(382) treated a group of 40 homosexual men (early-stage dementia
and mean CD4 cell counts of 500 cells/mm3)
with 1000 or 2000 mg/day of zidovudine or placebo. They
found that both treatment groups demonstrated significant combined
mean neuropsychological z score improvements when compared to the
placebo group. In another randomized, placebo-controlled clinical
trial, Schmitt and colleagues (383) used zidovudine to treat 281
subjects who did not necessarily have clear-cut signs of neuropsychological
impairment or cognitive disorder but were stratified into two groups,
AIDS or early asymptomatic HIV infection, on the basis of CD4 cell
count. Significant improvements were found in attention, memory,
visual-motor, and simple motor function at 4 months in both groups, which
led to premature discontinuation of the study.
An open study of zidovudine in injection drug users found
improvements in neuropsychological functioning on a number of subtests
(384). Four case control studies retrospectively examined whether
zidovudine treatment was associated with outcomes such as reduced
leukoencephalopathy (385, 386), lower CSF 2-microglobulin
levels (which are related to neuropsychological improvement) (387),
or improved neuropsychological measures (388). Three of the four
studies found that the zidovudine-treated patients had significantly
positive findings compared to untreated patients.
While the above studies support the efficacy of zidovudine,
they do not resolve the issue of optimal dosage nor zidovudine resistance
(380). Doses of up to 2000 mg/day of zidovudine were used
in some of the above studies, which are often associated with significant
toxicity, including neutropenia and anemia. A typical zidovudine
dose used now is 500–600 mg/day, and many patients
cannot tolerate even these reduced doses (375). Patients can develop
resistance to zidovudine, especially if used alone, and because
zidovudine-resistant strains can be transmitted from one person
to another, some HIV experts have considered the need for testing
for zidovudine resistance before choosing which agents to use in
treatment (389).
Treatment studies of antiretroviral agents other than zidovudine
are fewer but illuminating. De Ronchi and colleagues (390) conducted
a clinical trial (N=88) that compared zidovudine to didanosine
to refusal of therapy in both symptomatic and asymptomatic HIV patients.
They found that for subjects who were symptomatic for
HIV disease, both zidovudine and didanosine treatment
resulted in better performance on all neuropsychological
subtests. In general, asymptomatic subjects
did not show significant differences in neuropsychological performance
compared to the untreated group. The findings suggest differences
in effectiveness based on HIV clinical status.
A more recent placebo-controlled study involved the use of
abacavir, a nucleoside analogue reverse transcriptase
inhibitor with good CSF penetration, in 99 subjects with moderate
to severe HIV-associated dementia (391). This study did not demonstrate
significant differences in neuropsychological scores between abacavir
and placebo groups, but a major limiting factor in this study design
was that abacavir alone was added to an already failing antiretroviral
treatment regimen.
Of currently available antiretroviral agents, the CSF penetration
of stavudine is relatively high (0.4 ratio with serum), but a recent
study indicated that stavudine nevertheless penetrates brain tissue poorly
(392). The individual protease inhibitors have not been well studied
for effects on neurocognitive impairment, and all but indinavir
(0.16 ratio with serum) penetrate the CSF poorly (393). Regarding
the nonnucleoside reverse transcriptase inhibitors, nevirapine has
been shown to have a 0.45 CSF-to-serum ratio and therefore may be
a good candidate to include in future controlled studies of
HIV-associated cognitive disorders (381).
Ferrando and colleagues (394) studied the effects of various
combination antiretroviral therapy regimens on measures
of cognitive motor function. They found that tests of attention,
concentration, psychomotor speed, learning, and memory were significantly
better in those subjects taking antiretroviral therapy than in those
who were untreated. Furthermore, they found that those without neuropsychological
impairment had lower mean viral load levels, which suggests that
antiretroviral treatment benefits neuropsychological functioning
through lowering viral load. A similar conclusion was offered by
Sacktor et al. (40).
A few studies have examined the use of antiretroviral medications
to prevent HIV-associated dementia. Moore and colleagues (395) conducted
a study of 863 homosexual men treated with zidovudine who were evaluated
every 2 months for 2 years or until death. Development of HIV-associated
dementia continued with zidovudine treatment but was significantly
correlated with low CD4 cell count. Montforte and colleagues (396)
used didanosine in a study of 1,047 subjects (median CD4 cell count
of 47 cells/mm3 and mean prior
zidovudine treatment of 19 months). Subjects were followed every
2 months to a clinical endpoint (AIDS-defining condition, severe
adverse event, or death). They reported a very low incidence of
HIV-associated dementia (11 subjects, or 1%), although
no formal criteria for defining HIV-associated dementia were offered.
One randomized clinical trial with 32 subjects that compared zidovudine
treatment to placebo found no significant difference in rate of
developing dementia by treatment assignment (397). HIV-associated
dementia prevention requires further study, but it appears that
treatment with antiretroviral medications may prevent the development
of HIV-associated dementia and other cognitive motor disorders.
Although peptide T can be thought of as "antiretroviral," since
it blocks the binding of envelope glycoprotein to CD4 receptors,
it more likely exerts its effects through decrements in the deleterious effects
of inflammatory mediators known as cytokines, such as tumor necrosis
factor. A multisite, randomized, placebo-controlled clinical trial
with intranasal peptide T was conducted on a sample of 215 patients
with HIV-associated neurocognitive impairment, most of whom were
taking a single antiretroviral agent or a two-drug combination
regimen (398). The study found no statistically significant differences
between treatment and placebo groups on global neuropsychological
z scores. However, subgroup analyses showed that subjects with a
CD4 count of 201–500 cells/mm3 and
subjects with at least moderate neuropsychological impairment at
baseline improved significantly with peptide T compared with those
given placebo (p<0.05). In addition,
peptide T was well tolerated with no clinically significant toxic
Studies of inflammatory mediators are indicated because researchers
have postulated that HIV-related neuronal injury involves the activation
of voltage-dependent calcium channels and N-methyl-d-aspartate
(NMDA) receptor-operated channels (399). Therefore, studies are underway
using memantine (an NMDA antagonist), inhibitors of tumor necrosis
factor-, thalidomide, pentoxifylline,
and naloxone (an inhibitor of interferon-).
Mapou and colleagues (400) conducted a clinical trial with interferon--n3
in 20 asymptomatic subjects with HIV infection and reported significant
improvements in neuropsychological performance in selected
subtests. While interferon has been associated with neuropsychological
side effects, including depression, Skillman et al. (401) reported
that such side effects are minimal.
Nimodipine is a voltage-dependent calcium channel antagonist
that has been postulated to prevent HIV-related neuronal injury.
Two controlled studies of nimodipine, one in combination with zidovudine
(402) and one with nimodipine alone (403), found no significant
differences in overall neuropsychological performance.
Stimulant drugs have been used as palliative agents to help
manage symptoms of fatigue, decreased concentration, or
memory deficits among patients with HIV-associated dementia
or minor cognitive motor disorder. With regard to the specific effect
of stimulants on neurocognitive impairment, there has been one randomized,
placebo-controlled clinical trial of a small sample of eight opioid-dependent
patients maintained on a regimen of methadone (404). This 7-day
crossover study with sustained-release methylphenidate (20–40
mg/day) resulted in nonsignificant neuropsychological z
score improvements from baseline with methylphenidate but not placebo.
Fernandez and colleagues (321) presented case reports of treating
patients with HIV-related disease with methylphenidate (30–90
mg/day) or dextroamphetamine (30–60 mg/day).
All patients improved significantly; however, there was no placebo
control group and the sample size was small. Similar data from a
small trial are offered by Holmes et al. (405).
Studies of dopaminergic agonists are supported by preliminary
data in the form of case studies of carbidopa and l-dopa
(303). The Dana Consortium conducted a randomized, placebo-controlled
clinical trial of 36 subjects with HIV-associated cognitive motor
impairment who were given l-deprenyl,
a putative antiapoptotic agent, and found that deprenyl-treated
subjects showed an improvement in neuropsychological test performance,
specifically in verbal memory (406). Investigation of the dopaminergic
agent pramipexole is currently under way.
Other neurotransmitters such as serotonin and 5-hydroxyindoleacetic
acid have been found to be decreased in CSF as HIV disease progresses
(407). It is possible that increasing CNS serotonin levels through
administration of agents such as SSRIs may be useful in the treatment
of cognitive motor impairment.
Nutritional therapies need to be considered as potential interventions
for the cognitive motor symptoms associated with HIV infection.
A case report of a subject with apparent late-stage HIV-associated
dementia and a low cobalamin (vitamin B12)
level due to decreased intrinsic factor secretion responded over
2 months to B12 replacement therapy with
complete symptom resolution (408). Oxidative free radical scavengers such
as vitamin E, the experimental antioxidant OPC-14117, and the trace
mineral and antioxidant selenium may prove to be therapeutically
Antipsychotic medications have been the treatment of choice
in treating delirious states that develop in patients with HIV infection,
with most evidence arising from case reports or uncontrolled trials
(409, 410). For patients with HIV infection, a prominent issue is
the observed increased sensitivity to side effects (299, 300). This
sensitivity applies to extrapyramidal side effects with higher-potency
agents and also to cognitive side effects with lower-potency antipsychotics.
To date, only one randomized clinical trial has studied the
treatment of delirium associated with HIV infection. Breitbart and
colleagues (46) approached 244 hospitalized AIDS patients and monitored
them for the development of delirium. Among the 30 subjects who
went on to develop delirium, 310 episodes of delirium occurred that
met both DSM-III-R and Delirium Rating Scale criteria (411). The
30 subjects were randomly assigned to receive haloperidol (N=11),
chlorpromazine (N=13), or lorazepam (N=6). Because
the six subjects taking lorazepam developed signs of toxicity (oversedation,
disinhibition, ataxia, and increased confusion), this treatment
was terminated prematurely. Both haloperidol and chlorpromazine
treatment resulted in significantly reduced scores on the Delirium
Rating Scale in the first 24 hours. The researchers did not report
significant problems with extrapyramidal side effects in study patients,
but mean daily doses were low.
Scattered case reports or series suggest that other antipsychotic
agents may be useful for treating HIV-associated delirium. For instance,
molindone (312), risperidone (315), and droperidol (412, 413) have
been suggested as alternatives to the standard antipsychotic medication
because of differences in side effect profile, onset of action,
or potency.
Disturbances of mood occur frequently in the context of HIV
infection. Treatment studies are quite varied with regard to variables
such as severity of mood disorder, methodology to categorize or
diagnose mood disorders, outcome measures, and stage of HIV illness.
Many studies, including randomized controlled trials, open-label
trials, case series, and case reports, support the efficacy
and safety of many antidepressants in the acute treatment
of depressive disorders, including major depression, in a wide range
of HIV-infected populations at all disease stages.
Wagner and colleagues (286) reported on a series of 6-week
studies that used random assignment and placebo control to examine
the efficacy of standard and alternative antidepressants for major depression
in HIV-infected patients. The agents used at standard doses were
fluoxetine, sertraline, imipramine, dextroamphetamine, and testosterone.
Response rates to the different agents ranged from 70% to
93% and were significantly higher than placebo.
Similar findings were reported in a randomized, placebo-controlled
clinical trial conducted by Elliot and colleagues (287) in 75 HIV
patients (45% with AIDS) who had major depression. Both imipramine-
and paroxetine-treated groups improved significantly compared to
placebo at weeks 6, 8, and 12. The dropout rate due to side effects
was higher for those receiving imipramine (48%) than it
was for placebo (24%) or paroxetine (20%).
One randomized, placebo-controlled clinical trial (N=120)
found that fluoxetine was an efficacious antidepressant agent among
depressed HIV patients; the response rate for fluoxetine was 74% versus
47% for placebo (289). The same study reported significant
differences between ethnic groups in terms of antidepressant efficacy;
the response rates were 84% for white, 67% for
Latino, and 50% for black subjects (414). Despite the effectiveness
of fluoxetine in treating depression, because both placebo response
and attrition were high, the researchers suggested that the addition
of another medication in patients with serious medical illness who
require multiple concomitant medications may be a significant barrier
to the treatment of depression.
In a double-blind, placebo-controlled trial that compared
desipramine to fluoxetine in 14 women with advanced HIV
disease, both agents were linked to symptom improvement; however,
for most of the women significant depressive symptoms remained after
the 6-week trial (294). These findings are consistent with those
of an open-label fluoxetine trial that compared HIV-positive and
HIV-negative depressed men, which found that improvement in the
HIV-positive cohort was significantly delayed beyond the
8-week trial compared to the HIV-negative patients (415).
The randomized trials are supported by uncontrolled studies
of depression in HIV populations and confirm the effectiveness of
fluvoxamine (295) and fluoxetine (293, 416, 417) in HIV-infected asymptomatic patients
and of paroxetine, sertraline, and fluoxetine in symptomatic HIV
patients (285, 418). In an open trial in which HIV-positive depressed
women were given either fluoxetine or sertraline, both drugs were
found to be effective treatments (419). Another open-label study
found nefazodone effective in the treatment of depressed
HIV-positive patients (288). One open-label trial of 32 patients
with advanced HIV disease found venlafaxine effective among depressed
patients who also had minor cognitive motor disorder (420).
The use of psychostimulants for treatment of major depression
in HIV-infected outpatients has been supported in smaller studies,
including five case reports, one open-label trial, and one placebo-drug-placebo
clinical trial (321, 322, 421, 422). These studies suggest that
methylphenidate, up to 35 mg/day, or dextroamphetamine,
up to 10 mg/day, can improve major depression.
An open trial of testosterone replacement for hypogonadal
men found that of 34 study participants with major depressive disorder,
79% had significant improvement in mood (126). There is
a case report of a patient with HIV infection and comorbid major
depressive disorder whose depression resolved with treatment with
the antiretroviral agent zidovudine (423). For patients with severe
major depression who are delusional or have failed medication treatment,
ECT has been found to be safe and effective (424).
Several studies of psychotherapeutic treatment of depression
in HIV patients have been conducted. In a randomized, controlled
trial, Targ and colleagues (425) compared structured group therapy
plus fluoxetine to structured group therapy with placebo in 20 asymptomatic
homosexual men with major depression or adjustment disorder and
Hamilton Depression Rating Scale scores 16.
Both groups showed significant improvements in depression after
6 weeks of treatment, but there were no differences between treatment
groups (425). In contrast, another randomized, placebo-controlled
clinical trial that compared the efficacy and safety of fluoxetine
plus group psychotherapy versus group psychotherapy alone in 47
depressed HIV-positive men for 7 weeks found that fluoxetine
in addition to group therapy was more efficacious than group psychotherapy
alone. Differences were particularly apparent for patients
whose initial depressive episodes were rated as severe
(Hamilton depression score 24)
Markowitz and colleagues (426) conducted a randomized, placebo-controlled
clinical trial that compared 16-week interventions with interpersonal
psychotherapy, cognitive behavior therapy, supportive psychotherapy,
and supportive psychotherapy plus imipramine in 101 HIV
patients with depressive symptoms (Hamilton depression score 15).
Patients randomly assigned to interpersonal psychotherapy and supportive
psychotherapy plus imipramine had significantly greater symptom
improvement than those receiving supportive psychotherapy alone
or cognitive behavior therapy.
In an earlier study (427), the Markowitz group demonstrated
the benefits of interpersonal psychotherapy in HIV-positive, asymptomatic
outpatients in an open study of men and women with DSM-III-R major
depression or dysthymia. Twenty (87%) out of 23 patients
achieved a full remission after 6 weeks by clinical assessment;
mean Hamilton depression scores at baseline and follow-up were 25
and 6.8, respectively. Levine et al. (428) reported that four outpatients
with major depression remained euthymic for 9 months with
structured group psychotherapy after acute remission was achieved
with fluoxetine, 20–40 mg/day.
Other studies such as two retrospective chart reviews (284, 429) and a prospective effectiveness study (430) support the findings
from controlled and uncontrolled treatment studies of major depression
that treatment with a number of different antidepressant agents
is effective and generally tolerated in HIV patients.
Other studies have investigated the efficacy of treatment
for other types of depression in HIV patients. These studies generally
use screening instruments (e.g., the Center for Epidemiologic Studies
Depression Scale [CES-D Scale]) rather than structured
interviews or clinical evaluations to diagnose specific depressive
disorders. All involved ambulatory patients who had no significant clinical
manifestations of HIV disease. In a study of patients with depression
(CES-D Scale score >16) but with unknown psychiatric diagnoses,
investigators compared cognitive behavior therapy and brief supportive
group therapy to a waiting list control condition. Outpatients
(N=68) were randomly assigned to an 8-week intervention
of cognitive behavior therapy, support group, or a control group.
While both types of psychotherapy were superior to the control condition,
neither led to significant reductions on the CES-D Scale into the
nondepressed range (431).
Eller (432) conducted a randomized, placebo-controlled clinical
trial of alternative therapies for depression and assigned 81 male
and female outpatients with HIV infection to guided imagery, relaxation
therapy, or usual care. The sample had a mean CES-D Scale score
of 19. There were no significant declines in CES-D Scale scores
during treatment in any of the three groups.
One chart review (433) and one case report (434) have addressed
the treatment of manic syndromes in HIV-infected patients. The chart
review study identified seven male outpatients with mania who did
not improve with lithium or neuroleptic treatment due
to toxicity. Three patients had been treated with valproic acid
(750–1750 mg/day), two with clonazepam (2 mg/day),
one with phenytoin, and one with carbamazepine. All seven patients
experienced remission of their manic syndrome with the agent used
(433). The case report described the effectiveness of valproic acid
in the treatment of acute mania in a patient with AIDS complicated
by dementia (434). There are no published studies of maintenance
treatments for mania or bipolar disorders in HIV-infected populations.
Clinical consensus has established the necessity of treating
substance use disorders in order to produce optimal psychiatric
and medical outcomes for patients with HIV infection. Despite this knowledge,
remarkably few studies have investigated psychiatric treatment of
substance use disorders in HIV-infected patients. This section will
review the literature of the treatment of substance use disorders
and associated syndromes.
Entry into a treatment program is probably one of the more
critical steps for the assessment and treatment of substance use
disorders. Guydish and colleagues (435) described a consultation-education-triage
model program that referred drug users with HIV infection to follow-up
care for substance use disorders. Of the 86 patients referred over
an 8-month period, 81% were referred for further care to
a substance use program, with 58% actually contacting the
referral resource. Eighty percent had AIDS or symptomatic HIV disease;
37% of patients were dependent on alcohol, 36% were
dependent on amphetamines, and 26% were dependent on heroin,
marijuana, or cocaine.
The Program for AIDS Counseling and Education in San Francisco
is considered a model program for inner-city, poor, opiate-dependent,
mostly minority men (436, 437). The program provides medical assessment
and care, psychiatric treatment, methadone treatment,
counseling, detoxification, and tolerance management for opiate
addicts. Outcomes for patients enrolled in the Program for AIDS
Counseling and Education have been reported in two conference papers.
In one report, 29 opioid-dependent HIV patients with a mean of 28
days of drug use in the past month reduced their use to a mean of
5.9 days of use per month after 3 months in the program
(438). The other report focused on clinical events related to drug
use before and after enrollment for 62 patients in the program
(439). Clinical events included medical complications and lapses
in compliance with treatment. At baseline, patients experienced
0.72 clinically significant medical complications per 100 patient
years, whereas the rate decreased significantly to 0.16 during enrollment
in the Program for AIDS Counseling and Education. There was also
a reduction in preventable HIV clinical events from 0.21 per 100
patient years to 0.02 per 100 patient years after starting the program.
The reports provide some evidence that both the medical care as
well as substance use behaviors of HIV-infected opioid addicts can
benefit from a multidisciplinary, structured intervention.
One study of HIV-infected patients investigated the effect
of antidepressant medications on symptoms of drug dependency, such
as drug craving and comorbid depression. Batki (440) conducted a
controlled trial that compared fluoxetine to placebo in 37 patients
with cocaine and opiate dependency who were on a regimen of methadone
maintenance. Of this sample, 41% also had major depression.
Participants treated with fluoxetine (20–40 mg/day)
had lower median measures of cocaine metabolites in urine and fewer
mean days of cocaine use per week (1.6) compared to those given
placebo (2.6); the fluoxetine-treated patients also reported reduced
cocaine craving. Those with major depression showed significant
improvement after the 12-week treatment.
Lyketsos and colleagues (430) conducted a 14-month prospective
effectiveness study of clinical outcomes in HIV patients
who were referred to psychiatric treatment. Within the cohort, 110
patients had current (N=66) or recent (N=44) substance
use disorders; there were high rates of polysubstance dependence,
with only a small proportion of patients who abused alcohol. The
psychiatric treatment took place within a primary care clinic and
included treatment for substance abuse and concurrent psychiatric
disorders. Psychiatric intervention led to a decrease in the use
of substances and better clinical condition.
Anxiety disorders are prevalent in the population of persons
who have or are at risk for HIV infection, but studies of specific
treatments for anxiety disorders in HIV patients are lacking. The literature
provides only one retrospective chart review and two case reports
that address the management of anxiety disorders in HIV-positive
patients. There are no treatment studies of PTSD among HIV-infected
patients, although PTSD rates are high in some HIV-affected groups
A chart review study found that buspirone was an effective
anxiolytic in opioid-dependent, HIV-positive patients who were on
a regimen of methadone maintenance and who also had a comorbid anxiety
disorder. The study additionally showed a modest reduction of urine
tests positive for substances of abuse, from 42% to 30% (328).
McDaniel and Johnson (442) found fluoxetine to be effective
in the treatment of obsessive-compulsive disorder (OCD) in two HIV-positive
patients. Both patients tolerated the fluoxetine with minimal side
effects and responded with resolution of OCD symptoms within 6–8
A male patient with advanced AIDS complicated by comorbid
trichotillomania and major depression was reported to have responded
well to sertraline at a maximum dose of 150 mg/day. The patient
reported experiencing a 70%–80% decrease
in hair pulling and a modest improvement in depressed mood, with
minimal medication side effects (443).
Nine literature citations, two of them clinical trials and
the remainder case reports, present evidence concerning the efficacy
of psychotropic medication for the management of psychosis in the presence
of HIV infection. The nine reports contain fewer than 100 subjects,
approximately 90% of them male, and most with symptomatic
HIV infection, usually AIDS. Where stated, the majority did not
have a history of psychosis before HIV infection, and, where stated,
the majority had cognitive impairment.
Antipsychotic medications were effective in treating psychosis
whether or not cognitive dysfunction or delirium was present. One
large case history series found that patients with manic psychosis showed
more improvement than patients with schizophreniform psychosis (315).
The two clinical trials (31, 444) found that positive symptoms responded
better than negative symptoms. Across studies the subjects, who
largely had advanced HIV disease, required lower doses of antipsychotic medication,
similar to the pattern seen in the elderly. Lower doses were also
useful due to increased sensitivity to side effects. If a patient
did not respond to or tolerate one antipsychotic, it was useful to
try another from a different class (300, 301, 310, 312).
In case reports, the use of adjunctive medications, including
antianxiety drugs, antidepressants, and mood stabilizers, was a
common practice and often useful in individual cases, but there
have been no controlled studies on the efficacy of these combinations.
Two case reports, each of a single male subject with AIDS, found
that catatonia responded rapidly to lorazepam (445, 446). No side effects
were noted.
Maintenance medication was not always necessary to sustain
remission of psychotic symptoms (42, 312). In some cases it was
specifically noted that symptoms of psychosis diminished as severe late-stage
medical illness progressed (42). While it has been hypothesized
that there is a window of vulnerability to psychosis or mania occurring
early in the course of HIV-associated dementia (447), no data support
this theory, and most patients treated for psychosis have continued
their maintainance medication regimens.
There are few data on the treatment of psychosis in early-stage
HIV infection or among women nor is there information concerning
potential modifications in the treatment of preexisting psychotic illness,
which might be necessary in the presence of advancing HIV infection.
Two open-label clinical trials have assessed the effectiveness
of psychotropic medications in the management of adjustment disorders
in HIV-positive patients. As part of a larger study that examined the
effectiveness of paroxetine in the treatment of depression in the
context of HIV infection, Grassi and colleagues (418) included five
patients with a diagnosis of adjustment disorder with depressed mood.
All five patients received paroxetine (20 mg/day) and showed
significant recovery as measured by the Hamilton depression
scale at the 6-week endpoint.
Five male patients with neurocognitive impairment as well
as a diagnosis of adjustment disorder with depressed mood were treated
as part of a larger study of the effectiveness of psychostimulants in
patients with HIV-associated dementia. Four of the five patients
who received methylphenidate had moderate to marked improvement
in symptoms; the one patient with minimal response was switched
to dextroamphetamine and subsequently had a moderate response (405).
Numerous reports have documented disrupted sleep and altered
sleep architecture in HIV patients (29, 448, 449), including one
study which linked fatigue and sleep disturbances to morbidity and disability
in homosexual men (450). While the etiologies remain unclear, some
investigators have documented growth hormone dysregulation associated
with sleep pathology (451), and one study found obstructive sleep
apnea due to adenotonsillar hypertrophy to be a primary cause of
sleep disruption in a cohort of HIV patients with excessive daytime
sleepiness (452).
The treatment of sleep disorders in HIV-positive persons has
been examined in only one open-label clinical trial of flurazepam
in 12 patients (453). All patients were given a one-time dose of flurazepam,
30 mg, to examine changes in the patients' electroencephalographic
recordings during sleep. Flurazepam mainly affected non-REM parameters,
such as reduction of times awake during the night and increases
in stage two and effective sleep time. As this study did not address
treatment with flurazepam beyond a one-time dose, actual
treatment recommendations cannot be made.
Since HIV infection in childhood is associated with developmental
delays or loss of acquired skills, it is hoped that early treatment
will promote normal development. Currently, it appears that antiretroviral
drug therapy reduces morbidity in children, especially in those
with HIV-associated neurocognitive impairment. Several studies have
reported a significant increase in mental ability, as measured by
the WISC-R, the McCarthy Scales of Children's Abilities,
or the Bayley Scales of Infant Development, in over 450 children
during 12- and 36-month trials with zidovudine (58, 246, 454, 455).
None of the studies included a control group.
The safety of zidovudine for children is similar to that for
adults, although up to 40% of children experience hematological
side effects that require dose alterations (246). The one published
study of 54 children that did not find a significant improvement
in cognitive functioning with zidovudine treatment did find a significant
decrease in CD4 levels over the treatment period. No data were provided
on adherence to treatment or zidovudine resistance (456). Other
antiretroviral agents, such as didanosine, have been studied, with
a multisite project showing that combination zidovudine and didanosine
therapy was superior to either used as monotherapy for most of the
CNS outcomes evaluated (457). Although combination antiretroviral
therapy with three agents is standard practice with adults, there
is only one case report of its use with a child (458). Caregivers
noted the positive impact of this regimen on an 8-year-old boy's
neurocognitive development.
The effectiveness of the treatment of other mental and behavioral
disorders associated with HIV infection in children and adolescents
is largely unstudied. Case reports of single patients suggest that attention
deficit disorders and depressive disorders in those with HIV infection
may be treated by using regimens that are standard for those without
HIV infection (459). As in the treatment of adults, children with
HIV infection may be especially sensitive to some treatment side
effects, such as insomnia or appetite suppression associated with
psychostimulant use.
Pain frequently accompanies pediatric HIV and can involve
multiple organ systems (460). Clinicians should be aware that the
inadequate verbal skills of younger children or the fact that some children
are from non-English-speaking families can lead to the underrecognition
and undertreatment of pain (461).
A number of HIV-associated clinical syndromes have psychiatric
implications, such as wasting syndrome, fatigue, pain, and sexual
dysfunction. Because there are overlapping symptoms with these conditions
and psychiatric disorders, it is useful for psychiatrists to be
aware of treatment studies for such syndromes so that overall clinical
outcomes can be improved.
Several studies have focused on the use of testosterone for
treatment of wasting syndrome in both patients with low testosterone
levels and patients with "clinical hypogonadism" (normal
hormone levels). Grinspoon and colleagues (462) conducted a double-blind,
placebo-controlled study of hypogonadal HIV-positive men
with wasting syndrome that demonstrated the safety and efficacy
of testosterone replacement therapy (300 mg i.m. every 3 weeks).
The treatment resulted in a significant increase of lean body mass,
overall quality of life, and self-perception of appearance in treated subjects.
Similar findings have been reported by Rabkin and colleagues (126, 343, 463), who conducted several randomized, placebo-controlled
trials as well as open trials of testosterone replacement in men
with clinical hypogonadism that led to significant positive
effects on mood and weight (lean body mass). Another study that
used oxymetholone, a testosterone derivative, demonstrated weight
gain in cachectic men with AIDS (464). A controlled study of hypogonadal women with
HIV infection that used transdermal testosterone replacement also
reported improvement in lean body mass and quality of life (465).
Wagner and colleagues (466) reported an additional improvement
of measures on the Brief Symptom Inventory and nutritional status
for patients who exercised in addition to receiving testosterone
replacement. In a double-blind, randomized, placebo-controlled trial,
researchers found that resistance exercise in addition to testosterone
and the anabolic steroid oxandrolone substantially increased lean
body mass (467). Two open-label studies have reported that oxandrolone,
20 mg/day, in HIV patients with wasting syndrome led to
significant weight gain, in particular, increases in body cell mass
(334, 335).
Several clinical trials have used the recombinant growth hormone
somatotropin for treatment of HIV-related wasting (336, 340). A
large multicenter, double-blind, placebo-controlled study that used growth
hormone in patients with AIDS wasting reported significant improvement
in overall quality of life and weight gain, with no negative effect
on virological or immunological markers (339). Treatment was well
Since tumor necrosis factor- has
been postulated to have a role in the pathogenesis of wasting syndrome,
the effect of thalidomide, a selective inhibitor of tumor necrosis
factor-, has been studied in patients
with AIDS wasting syndrome. Two reports (a mail survey of thalidomide
users and a small randomized, placebo-controlled clinical
trial) have supported the positive effects of thalidomide on weight
gain, appetite, and quality of life (341, 342).
Breitbart and colleagues (468) conducted a randomized, placebo-controlled clinical
trial that used two psychostimulant medications, methylphenidate
and pemoline, in treating fatigue among HIV patients. They found
that both treatments were superior to placebo, with a stronger effect
in the methylphenidate group. In addition, they reported that improvement
in fatigue was associated with improvement in depressive symptoms
and psychological distress. In an open trial of depressed patients
with CD4 counts below 200, dextroamphetamine administration led
to improvement of fatigue in 95% of patients along with
reduction in depression scores (322). Testosterone replacement with
dehydroepiandrosterone (DHEA) in HIV-infected hypogonadal men has
also been found to improve symptoms of fatigue (469).
Studies of the frequency and adequacy of treatment for pain
among patients with AIDS find wide variations in the effectiveness
of interventions to manage pain. A study by Breitbart et al. (123)
found that 85% of HIV patients in their ambulatory sample
treated at a cancer center received inadequate pain therapy. Yet
a different study reported that only 20% of their sample
of AIDS patients treated in the hospital, home care, or nursing
facility did not receive effective pain control (470).
While agents such as tricyclic antidepressants and anticonvulsant
medications are often used to manage chronic pain from peripheral
neuropathy, published treatment studies for HIV-associated peripheral
neuropathy have not supported their use. Two randomized, controlled
trials have focused on HIV-associated peripheral neuropathy; both
trials used the agent mexiletine, an antiarrhythmic drug with local
anesthetic properties that had been used in the treatment of diabetic
neuropathy (317, 471). Neither study found pain relief different
from that of placebo. Furthermore, Kieburtz et al. (317) did not
find that treatment with amitriptyline provided significant pain
relief compared to placebo. Shlay and colleagues (472) conducted
a randomized, controlled trial that compared acupuncture, amitriptyline,
and placebo for pain due to HIV-related peripheral neuropathy and
found that neither acupuncture nor amitriptyline was more effective
than placebo.
Sexual dysfunction is experienced commonly by HIV patients,
both men and women, particularly with HIV disease progression. While
no treatment trials are currently published, a cautionary note regarding
sildenafil is clinically important. Sildenafil should be used judiciously
in patients with erectile dysfunction who are also taking protease
inhibitors, since the primary route of sildenafil metabolism is
via the cytochrome P450 isoenzyme 3A4. One death has been reported
in a 47-year-old male taking ritonavir and saquinavir who was administered
25 mg of sildenafil (473). The manufacturer of sildenafil
has recommended that patients receiving ritonavir
should not take more than a single sildenafil dose of 25 mg in a
48-hour period.
Considerable progress has been made in understanding HIV,
AIDS, and treatment for these conditions. However, further studies
are needed regarding specific, effective treatments for patients, including
women and children, with HIV/AIDS. Areas of specific concern
The impact of antiretroviral
therapy on the incidence of CNS opportunistic diseases and neuropsychiatric
The specific etiology of HIV-associated dementia and
minor cognitive motor disorder and effective interventions to prevent
or ameliorate these conditions.
The clinical significance of drug-drug interactions
of psychotropic agents and HIV-related medications.
Whether HIV is directly linked to the occurrence of
psychosis, mania, depression, or other psychiatric disorders in
persons with HIV infection.
Whether the CNS serves as a reservoir of HIV-resistant
strains and the clinical implications if it does.
The effectiveness of psychiatric care in critical areas
of treatment adherence, prevention of HIV infection, and psychosocial
Information about the impact of HIV infection on development
in children, with possible differences in clinical course due to
whether infected in utero or perinatally or due to type
of treatment received.
More effective interventions for HIV risk reduction
in specific psychiatric populations, particularly for primary prevention
of HIV infection.
The need for more data about the effectiveness of psychiatric
treatments such as psychotherapy, pharmacotherapy, and psychosocial
services for adults, adolescents, and children with HIV/AIDS.
Investigating possible gender differences in the problems
associated with HIV/AIDS and treatment for these conditions.
See Table.
General information
AIDS Action Committee (AAC)
AIDS Daily Summary
AIDS Education Training Centers (AETC)
AIDS Virtual Library
American Medical Association
American Psychiatric Association
Business and Labor Resource Service
Centers for Disease Control and Prevention
CDC National Prevention Information
Network (CDCNAC)
CDC National AIDS Funding Database
CMV Retinitis Education and Treatment
Food and Drug Administration (FDA)
FDA Medical Bulletin
Healthcare Communications Group
Human Retroviruses and AIDS Sequence
Johns Hopkins AIDS Service
Infectious Diseases Society
Insights in HIV Disease Management
Medical Matrix
National Academy of Sciences
National AIDS Treatment Advocacy Project
National Hemophilia Foundation (NHF)
National Institutes of Health (NIH)
National Science Foundation
New York Online Access on Health
Pharmaceutical Research Manufacturers
Association of America (PhRMA)
The Access Project
The Body
University of California HIV/AIDS
USP Pharmacopeia Practitioners Reporting
Yahoo: Health Medicines HIV/AIDS
Webber's AIDS/HIV
Law and Policy Resource
Alternative treatments
American Chiropractic Association
ATDN's Alternative Treatments
Bastyr University AIDS Research Center
Herb Research Foundation
Homeopathic Educational Services
Institute for Traditional Medicine
Clinical trials
Adult AIDS Clinical Trials Group (ACTG)
AIDS Clinical Trial Information Services
AIDS Treatment Information Service
American Foundation for AIDS Research
Canadian HIV Trials Network
Pediatric AIDS Clinical Trials Group
USA HIV Clinical Trials/Trial
Vanderbilt Vaccines
Harm reduction/ needle exchange
Center for AIDS Prevention Studies
The Lindesmith Center
The XCHANGE POINT
North American Syringe Exchange Network
Safe Works AIDS Project
Recreational drugs and anti-HIV drug
National AIDS Manual
Notes from the Underground
Positively AWARE
The Toronto Hospital
CATIE (Community AIDS Treatment Information
University of California, San Francisco
NO/AIDS Task Force
Project Inform
San Francisco AIDS Foundation
J. Atkinson, M.D.
Steven Batki, M.D.
Christy L. Beaudin, Ph.D., L.C.S.W., C.P.H.Q.
Carl Bell, M.D.
Marcia Bennett, D.N.S.
Alan Berkman, M.D.
Philip A. Bialer, M.D.
Charles H. Blackinton, M.D., P.A.
Mel Blaustein, M.D.
Michael T. Brady, M.D.
William Breitbart, M.D.
Robert Broadbent, M.D.
Robert Paul Cabaj, M.D.
Susan Chuck, Pharm.D.
Norman A. Clemens, M.D.
Dave Davis, M.D.
Steven A. Epstein, M.D.
Abraham Feingold, Psy.D.
Steve Ferrando, M.D.
Jack Gorman, M.D.
William M. Greenberg, M.D.
Susan Haikalis, L.C.S.W.
Mark Halman, M.D.
Lawrence Hartmann, M.D.
Roman M. Hendrickson, M.D.
Al Herzog, M.D.
Dan Hicks, M.D.
Ewald Horwath, M.D.
Michael Hughes, M.D.
Jeffrey S. Janofsky, M.D.
T. Stephen Jones, M.D.
Nalini V. Juthani, M.D.
Cheryl Ann Kennedy, M.D.
Robert Kertzner, M.D.
Lawrence Y. Kline, M.D.
Joyce Kobayashi, M.D.
Ronald R. Koegler, M.D.
Thomas Kosten, M.D.
Zev Labins, M.D.
Debra E. Lyon, Ph.D.
John C. Markowitz, M.D.
Elinore F. McCance-Katz, M.D.
Karen McKinnon, M.A.
Philip R. Muskin, M.D.
Judith Rabkin, M.D.
David Rosmarin, M.D.
Peter Ross
Pedro Ruiz, M.D.
Larry Siegel, M.D.
Robert Stasko, M.D.
William R. Tatomer, M.D.
Joshua T. Thornhill IV, M.D.
Glenn J. Treisman, M.D.
Milton L. Wainberg, M.D.
Bert Warren, M.D.
Jonathan L. Worth, M.D.
Claire Zilber, M.D.
American Academy of Family Physicians
American Academy of Psychiatry and the Law
American Group Psychotherapy Association, Inc.
American Psychiatric Nurses Association
American Society of Addiction Medicine
American Society of Clinical Psychopharmacology, Inc.
APA Commission on Psychotherapy by Psychiatrists
Association for Academic Psychiatry
Association of Gay and Lesbian Psychiatrists
Black Psychiatrists of America
National Association of Social Workers
PacifiCare Behavioral Health
Royal Australian and New Zealand College of Psychiatrists
The following coding system is used to indicate the nature
of the supporting evidence in the references:
clinical trial. A study of an intervention in which
subjects are prospectively followed over time; there are treatment
and control groups; subjects are randomly assigned to the two groups;
both the subjects and the investigators are blind to the assignments.
[B]Clinical trial. A
prospective study in which an intervention is made and the results
of that intervention are tracked longitudinally; study does not
meet standards for a randomized clinical trial.
[C]Cohort or longitudinal
study. A study in which subjects are prospectively
followed over time without any specific intervention.
[D]Case-control study. A
study in which a group of patients and a group of control subjects
are identified in the present and information about them is pursued
retrospectively or backward in time.
[E]Review with secondary
data analysis. A structured analytic review of
existing data (e.g., a meta-analysis or a decision analysis).
[F]Review. A
qualitative review and discussion of previously published literature
without a quantitative synthesis of the data.
[G]Other. Textbooks,
expert opinion, case reports, and other reports not included above.
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18. Descamps D, Flandre P, Calvez V, Peytavin G, Meiffredy
V, Collin G, Delaugerre C, Robert-Delmas S, Bazin B, Aboulker JP,
Pialoux G, Raffi F, Brun-Vezinet F: Mechanisms of virologic failure in
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20. Boden D, Hurley A, Zhang L, Cao Y, Guo Y, Jones E, Tsay
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