pediatrics
Human Immunodeficiency Virus (HIV) Infection in Infants and Children
Treatment of HIV Infection in Infants and Children
Combinations of antiretroviral (ARV) medications (antiretroviral therapy [ART]) Supportive care Combination ART is individualized to the child but most commonly includes 3 medications: Two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)plus One integrase strand transfer inhibitor (INSTI)orone protease inhibitor Sometimes a non-nucleoside reverse transcriptase inhibitor (NNRTI) is given with 2 NRTIs. Because of the success of combination ART, much of the current focus is on the management of HIV infection as a chronic disease, addressing both medical and social issues. Important long-term medical issues include the need to manage HIV-related and drug-related metabolic complications and to account for age-related changes in drug pharmacokinetics and pharmacodynamics. Social issues include the need to cope with peer pressure, ensure school success and appropriate career choice, and educate children about transmission risk. Adolescents often have difficulty seeking and following health care advice and need particular help with treatment adherence. Challenges for infants and younger children include lack of pediatric pharmacokinetic data for newer compounds, palatability and tolerability of liquid formulations, and lack of fixed-dosed combination tablets. Children and adolescents should be managed in collaboration with experts who have experience in the management of pediatric HIV infection. (For a discussion of some ARV medications and dosages, see Antiretroviral Therapy in Children and see the Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV's Initiation of ART for children is similar to that in adults; essentially, all children with HIV infection should be given ART as soon as possible (rapid initiation, within 1 to 2 weeks of diagnosis). There is both strong consensus and clinical trial evidence for early initiation of ART in infants with HIV infection. The goal of therapy at all ages is similar to that in adults: Suppress HIV replication (as measured by HIV plasma viral load). Maintain or achieve age-normal CD4+ counts and percentages with the least amount of drug toxicity. Before making the decision to initiate therapy, the practitioner should fully assess the readiness of the caregiver and child to adhere with ARV medication administration and discuss the potential benefits and risks of therapy. Because expert opinions on therapeutic strategies change rapidly, consultation with experts is strongly advised. ART is successful only if the family and child are able to adhere to a possibly complex medical regimen. Nonadherence not only leads to failure to control HIV but also selects drug-resistant HIV strains, which reduces future therapeutic choices. Barriers to adherence should be addressed before starting treatment. Barriers include availability and palatability of pills or suspensions, adverse effects (including those due to drug interactions with current therapy), pharmacokinetic factors such as the need to take some medications with food or in a fasted state, and a child’s dependence on others to give medications (and parents with HIV infection may have problems with remembering to take their own medications). Newer once- or twice-daily combination regimens and more palatable pediatric formulations help improve adherence, and the growing availability of once-daily fixed-dose combination tablets for older children and adults has helped many youth living with HIV infection. Adherence may be especially problematic in adolescents regardless of whether they have been infected perinatally or have acquired HIV infection later on through sexual activity or injection drug use. Adolescents have complex biopsychosocial issues, such as low self-esteem, chaotic and unstructured lifestyles, fear of being singled out because of illness, and sometimes a lack of family support, all of which may reduce ART adherence. In addition, adolescents may not be developmentally able to understand why ARV medications are necessary during periods of asymptomatic infection and they may worry greatly about adverse effects. Despite frequent contact with the medical system, perinatally infected adolescents may fear or deny their HIV infection, distrust information provided by the health care team, and poorly make the transition to the adult health care system (see Transition to Adult Care ). Treatment regimens for adolescents must be made in consideration of these issues. Although the goal is to have the adolescent adhere to a maximally potent regimen of ARV medications, a realistic assessment of the adolescent's maturity and support systems may suggest that the treatment plan begin by focusing on avoidance of opportunistic illness and providing information about reproductive health services, housing, and how to succeed in school. Once care team members are confident the adolescent is receiving proper support, they can decide exactly which ARV medications are best. Clinical and laboratory monitoring are important for identifying drug toxicity and therapeutic failure. At entry into care and at initiation of ART (and if changing ART regimen): Physical examination, adherence evaluation, complete blood count, serum chemistry values including electrolytes, liver and kidney tests, HIV plasma viral load, CD4+ lymphocyte counts, and, for adolescent girls, a pregnancy test Every 3 to 4 months: Physical examination, adherence evaluation, complete blood count, serum chemistry values, including electrolytes, liver and kidney tests, HIV plasma viral load, and CD4+ lymphocyte counts Every 6 to 12 months: Lipid profiles and urinalysis; complete blood count and serum chemistry values including electrolytes, and liver and kidney tests if not done already in those with a stable clinical status; adherence evaluation HIV genotypic resistance testing should be done at entry into care and upon ART changes due to presumed virologic failure. Ifabacaviris to be given, HLA-B*5701 status must be tested;abacavirshould be given only to patients who are HLA-B*5701–negative. This testing is most often done at entry into care so that safety of possible future use ofabacaviris known. If children have a stable treatment status, ie, nondetectable HIV RNA and normal age-adjusted CD4+ lymphocyte counts without clinical signs of toxicity for at least 12 months, and a stable family support system, many clinicians will extend the interval of laboratory evaluations to every 6 to 12 months. However, clinical care visits every 3 months with measurement of HIV plasma viral load are valuable because clinicians have the opportunity to review adherence, monitor growth and clinical symptoms, and update weight-based dosing of ARV medications as needed. Prophylactic treatment is recommended in certain children with HIV infection for prevention of Pneumocystis jirovecii Pneumonia and Prophylaxis againstPneumocystispneumoniais indicated for Children with HIV infection who are≥6 years of age with CD4+ count<200 cells/mcL or CD4+ percentage<14% Children with HIV infection who are 1 to < 6 years of age with CD4+ count<500 cells/mcL or CD4+ percentage<22% Infants with HIV infection who are<12 months of age regardless of CD4+ count or percentage Infants born to women with HIV infection (beginning at 4 to 6 weeks of age) until HIV infection is either presumptively excluded by documentation of 2 negative virologic test results (1 at≥2 weeks of age and 1 at≥4 weeks of age) or definitively excluded by documentation of 2 negative virologic test results (1 at≥1 month of age and 1 at≥4 months of age) (NOTE: For these definitions of HIV exclusion to be valid, the infant must not be breastfeeding.) Once immune reconstitution with combination ART occurs, discontinuation ofPneumocystispneumonia prophylaxis may be considered for children with HIV infection who have received combination ART for>6 months and whose CD4+ percentage and CD4+ count have remained higher than the previously described treatment thresholds for>3 consecutive months. Subsequently, the CD4+ percentage and count should be reevaluated at least every 3 months, and prophylaxis should be reinstituted if the original criteria are reached. The medication of choice forPneumocystisprophylaxis at any age istrimethoprim/sulfamethoxazole (TMP/SMX). The dosage is TMP 75 mg/SMX 375 mg/m2orally 2 times a day on 3 consecutive days/week (eg, Monday-Tuesday-Wednesday); alternative schedules include the same dose 2 times a day every day, the same dose 2 times a day on alternate days, or twice the dose (TMP 150 mg/SMX 750 mg/m2) once a day for 3 consecutive days/week. Some experts find it easier to use weight-based dosing (TMP 2.5 to 5 mg/SMX 12.5 to 25 mg/kg orally 2 times a day). For patients who cannot tolerate TMP/SMX,dapsone2 mg/kg (not to exceed 100 mg) orally once a day is an alternative, especially for those<5 years of age. Oralatovaquonegiven daily or aerosolizedpentamidine(300 mg via specially designed inhaler for children ≥ 5 years) given once a month is an additional alternative. IVpentamidinehas also been used but is less effective and more toxic. Prophylaxis againstM. aviumcomplexinfection is indicated in Children≥6 years with CD4+ count<50 cells/mcL Children 2 to 6 years with CD4+ count<75 cells/mcL Children 1 to 2 years with CD4+ count<500 cells/mcL Children<1 year with CD4+ count<750 cells/mcL Weeklyazithromycinor dailyclarithromycinis the medication of choice, and dailyrifabutinis an alternative. HIV infection in a child affects the entire family. Serologic testing of siblings and parents is recommended for those families with a child with perinatally acquired infection. This may not be necessary for those families without known HIV infection who adopt a child with HIV infection. The physician must provide education and ongoing counseling. Children with HIV infection should be taught good hygiene and behavior to reduce risk to others. How much and when children are told about the illness depends on age and maturity. Older children and adolescents should be made aware of their diagnosis and the possibility of sexual transmission and should be counseled appropriately. Families may be unwilling to share the diagnosis with people outside the immediate family because it can create social isolation. Feelings of guilt are common. Family members, including children, can become clinically depressed and require counseling. Because HIV infection is not acquired through the typical types of contact that occur among children (eg, through saliva or tears), children with HIV infection should be allowed to attend school without restrictions. Similarly, there are no inherent reasons to restrict foster care, adoptive placement, or child care of children with HIV infection. Conditions that may pose an increased risk to others (eg, aggressive biting or the presence of exudative, weeping skin lesions that cannot be covered) may require special precautions. The number of school personnel aware of the child’s condition should be kept to the minimum needed to ensure proper care. The family has the right to inform the school, but people involved in the care and education of a child with HIV infection must respect the child’s right to privacy. Disclosures of information should be made only with the informed consent of the parents or legal guardians and age-appropriate assent of the child. Childhood Vaccination Schedules (including for The main exception is thatlive-virus vaccines and live-bacteria vaccines(eg, bacille Calmette–Guérin [BCG]) should be avoided or used only in certain circumstances (see table). Live oral poliovirus vaccine (which is not available in the United States but is still used in other parts of the world) and live-attenuated influenza vaccine are not recommended; however, inactivated polio vaccine should be given according to the routine schedule, and Influenza Vaccine should be given yearly. The live Measles, Mumps, and Rubella (MMR) Vaccine and may be given to infants who are exposed to HIV or who are infected with HIV according to the Childhood Vaccination Schedules . Safety and efficacy data are limited in symptomatic infants but there very likely is overall benefit to immunization, particularly in areas where rotavirus causes significant mortality. The BCG vaccine is not recommended in the United States because it is an area of low tuberculosis (TB) prevalence. However, elsewhere in the world, especially in countries where TB prevalence is high, BCG is routinely used; many of these countries also have high HIV prevalence among childbearing women. BCG as a live bacterial vaccine has caused some harm in children with HIV infection but likely protects children who do not have HIV infection and even some children who do have HIV infection from acquiring TB. The World Health Organization (WHO) now recommends that children who are known to be HIV-infected, even if asymptomatic, should no longer be immunized with BCG vaccine. However, BCG may be given to asymptomatic infants of unknown HIV infection status born to women with HIV infection, depending on the relative incidence of TB and HIV in the particular area. BCG also may be given to asymptomatic infants born to women of unknown HIV infection status. In some areas of the world, children are routinely given the Prevention or the Because children with symptomatic HIV infection generally have poor immunologic responses to vaccines, they should be considered susceptible when they are exposed to a vaccine-preventable disease (eg, measles, tetanus, varicella) regardless of their vaccination history. Such children should receive passive immunization with IV immune globulin. IV immune globulin also should be given to any nonimmunized household member who is exposed to measles. should receive Poliomyelitis Vaccine rather than oral polio vaccine. Influenza (inactivated or live), MMR, varicella, and rotavirus vaccines may be given normally because these vaccine viruses are not commonly transmitted by the vaccinee. Adult household contacts should receive annual influenza vaccination (inactivated or live) to reduce the risk of transmitting influenza to the person with HIV infection. Additional recommendations for children with HIV infectionare 1 to 2 months after the last dose of the Hepatitis B (HepB) Vaccine series, children with HIV infection should be tested to determine whether the level of antibodies to hepatitis B surface antigen (anti-HBs) is protective ( Children and adolescents with HIV infection who are < 18 years of age should be given the Pneumococcal Vaccine . (See also Certain postexposure treatment recommendations also differ. Meningococcal Vaccine has been recommended for routine and catch-up use in children, adolescents, and adults with HIV infection (see also ACIP 1.Kobayashi M, Farrar JL, Gierke R, et al: Use of 15-valent pneumococcal conjugate vaccine among U.S. children: Updated recommendations of the Advisory Committee on Immunization Practices—United States, 2022.MMWR Morb Mortal Wkly Rep71(37):1174–1181, 2022. doi: 10.15585/mmwr.mm7137a3 