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Access to and use of HIV antiretroviral therapy: variation by race/ethnicity in two public insurance programs in the U.S.
Kahn, James G.
Zhang, Xiulan
Cross, Lanny T.
Palacio, Herminia
Birkhead, Guthrie S.
Morin, Stephen F.
Public Health Reports
OBJECTIVES: To examine access to and use of HIV highly active antiretroviral therapy (HAART) by race/ethnicity in Medicaid and the AIDS Drug Assistance Program (ADAP) in 1998 in four states. METHODS: The authors analyzed reimbursement claims and AIDS surveillance data in California, Florida, New York, and Texas. Study subjects were identified using diagnostic or medication codes specific to HIV. The race/ethnicity of program enrollees was compared to representation in the HIV epidemic to examine access. Claims for antiretroviral (ARV) use were compared to U.S. Public Health Service treatment guidelines to assess HAART use. RESULTS: The authors identified 151,000 HIV-infected individuals in these two programs in the four states. Evidence of AIDS or symptomatic HIV was present in 78%-88% of enrollees in Medicaid, versus 31%-48% in ADAP. African Americans participated in Medicaid 10%-53% above and in ADAP 17%-31% below representation in the epidemic. Non-Latino whites exhibited the opposite pattern, being in Medicaid 5%-38% below and in ADAP 9%-65% above epidemic representation. Latinos participated more in ADAP (7%-31%), except in New York. HAART use over 90 days (July-September) ranged from 38% to 76% by program and state. Differences by race/ethnicity were inconsistent and small: African Americans had lower HAART use by 6%-14% in California and Florida Medicaid, and Latinos had higher HAART use by 2%-11% in ADAP and in Texas Medicaid. CONCLUSIONS: African Americans were more likely to access HIV drugs through Medicaid than through ADAP, which may reflect differences in program eligibility criteria as well as care seeking later in HIV disease. Differences in the use of HAART by race/ethnicity within state programs were small.
Related Articles
State Variation in AIDS Drug Assistance Program Prescription Drug Coverage for Modifiable Cardiovascular Risk Factors
Blackstock, Oni J.
Wang, Karen H.
Fiellin, David A.
Journal of General Internal Medicine
In the United States, mortality from cardiovascular disease has become increasingly common among HIV-infected persons. One-third of HIV-infected persons in care may rely on state-run AIDS Drug Assistance Programs (ADAPs) for cardiovascular disease-related prescription drugs. There is no federal mandate regarding ADAP coverage for non-HIV medications.
To assess the consistency of ADAP coverage for type 2 diabetes, hypertension, hyperlipidemia, and smoking cessation using clinical guidelines as the standard of care.
Cross-sectional survey of 53 state and territorial ADAP formularies.
ADAPs covering all first-line drugs for a cardiovascular risk factor were categorized as "consistent" with guidelines, while ADAPs covering at least one first-line drug, but not all, for a cardiovascular risk factor, were categorized as "partially consistent". ADAPs without coverage were categorized as "no coverage".
Of 53 ADAPs, four (7.5%) provided coverage consistent with guidelines (coverage for all first-line drugs) for all four cardiovascular risk factors. Thirteen (24.5%) provided no coverage for all four risk factors. Thirty-six (68%) provided at least partially consistent coverage for at least one surveyed risk factor. State ADAPs provided coverage consistent with guidelines most frequently for type 2 diabetes (28%), followed by hypertension (25%), hyperlipidemia (15%) and smoking cessation (8%). Statins (66%) were most commonly covered and nicotine replacement therapies (9%) least often. Many ADAPs provided no first-line treatment coverage for hypertension (60%), type 2 diabetes (51%), smoking cessation (45%), and hyperlipidemia (32%).
Consistency of ADAP coverage with guidelines for the surveyed cardiovascular risk factors varies widely. Given the increasing lifespan of HIV-infected persons and restricted ADAP budgets, we recommend ADAP coverage be consistent with guidelines for cardiovascular risk factors.
Electronic supplementary material
The online version of this article (doi:10.1007/s11606-011-1807-5) contains supplementary material, which is available to authorized users.
AIDS; HIV; public assistance; AIDS drug assistance program; cardiovascular disease
Related Articles
Antiretroviral Treatment and Prevention of Peripartum and Postnatal HIV Transmission in West Africa: Evaluation of a Two-Tiered Approach
Tonwe-Gold, Besigin
Ekouevi, Didier K
Viho, Ida
Amani-Bosse, Clarisse
Toure, Siaka
Coffie, Patrick A
Rouet, François
Becquet, Renaud
Leroy, Valériane
El-Sadr, Wafaa M
Abrams, Elaine J
Dabis, François
PLoS Medicine
Highly active antiretroviral treatment (HAART) has only been recently recommended for HIV-infected pregnant women requiring treatment for their own health in resource-limited settings. However, there are few documented experiences from African countries. We evaluated the short-term (4 wk) and long-term (12 mo) effectiveness of a two-tiered strategy of prevention of mother-to-child transmission of HIV (PMTCT) in Africa: women meeting the eligibility criteria of the World Health Organization (WHO) received HAART, and women with less advanced HIV disease received short-course antiretroviral (scARV) PMTCT regimens.
Methods and Findings
The MTCT-Plus Initiative is a multi-country, family-centred HIV care and treatment program for pregnant and postpartum women and their families. Pregnant women enrolled in Abidjan, Côte d'Ivoire received either HAART for their own health or short-course antiretroviral (scARV) PMTCT regimens according to their clinical and immunological status. Plasma HIV-RNA viral load (VL) was measured to diagnose peripartum infection when infants were 4 wk of age, and HIV final status was documented either by rapid antibody testing when infants were aged ≥ 12 mo or by plasma VL earlier. The Kaplan-Meier method was used to estimate the rate of HIV transmission and HIV-free survival. Between August 2003 and June 2005, 107 women began HAART at a median of 30 wk of gestation, 102 of them with zidovudine (ZDV), lamivudine (3TC), and nevirapine (NVP) and they continued treatment postpartum; 143 other women received scARV for PMTCT, 103 of them with sc(ZDV+3TC) with single-dose NVP during labour. Most (75%) of the infants were breast-fed for a median of 5 mo. Overall, the rate of peripartum HIV transmission was 2.2% (95% confidence interval [CI] 0.3%–4.2%) and the cumulative rate at 12 mo was 5.7% (95% CI 2.5%–9.0%). The overall probability of infant death or infection with HIV was 4.3% (95% CI 1.7%–7.0%) at age week 4 wk and 11.7% (95% CI 7.5%–15.9%) at 12 mo.
This two-tiered strategy appears to be safe and highly effective for short- and long-term PMTCT in resource-constrained settings. These results indicate a further benefit of access to HAART for pregnant women who need treatment for their own health.
In an observational cohort study from Côte d'Ivoire, François Dabis and colleagues report on prevention of mother-to-child HIV transmission among women receiving antiretroviral therapy according to World Health Organization recommendations.
Editors' Summary
Effective treatments are available to prevent AIDS in people who are infected with HIV, but not everyone with HIV needs to take medication. Usually, anti-HIV medication is recommended only for those whose immune systems have been significantly affected by the virus, as evidenced by symptoms or by the results of a blood test, the CD4 lymphocyte ("T cell") count. Treating HIV usually requires a combination of three or more medications. These combinations (called HAART) must be taken every day, can cause complications, and can be expensive.
Worldwide, more than half a million children became infected with HIV each year. Most of these children acquire HIV from their mothers during pregnancy or around the time of birth. If a pregnant woman with HIV takes HAART, her chances of passing HIV to the baby are greatly reduced, but the possible side effects of HAART on the baby are not known. Also, most transmission of HIV from mothers to babies occurs in poor countries where supplies of HAART are limited. For these reasons, World Health Organization (WHO) does not recommend that every pregnant woman receive HAART to prevent HIV transmission to the baby, unless the woman needs HAART for her own health (for example if her T cells are low or she has severe symptoms of HIV infection). For pregnant women with HIV who do not need to take HAART for their own health, less complicated treatments, involving a short course of one or two HIV drugs, can be used to reduce the risk of passing HIV to the baby.
Why Was This Study Done?
The WHO recommendations for HAART in pregnancy are based on the best available evidence, but it is important to know how well they work in actual practice. The authors of this study were providing HIV treatment to pregnant women with HIV in West Africa through an established clinic program in Abidjan, Côte d'Ivoire, and wanted to see how well the WHO recommendations for HAART or short-course treatments, depending on the mother's condition, were working to protect babies from HIV infection.
What Did the Researchers Do and Find?
The researchers studied 250 HIV-infected pregnant women who received HIV medications in the Abidjan program between mid-2003 and mid-2005. In accordance with WHO guidelines, 107 women began HAART for their own health during pregnancy, and 143 women did not qualify for HAART but received other short course treatments (scARV) to prevent HIV transmission to their babies. The authors monitored mothers and babies for treatment side effects and tested the babies for HIV infection up to age 1 y.
They found that HAART was relatively safe during pregnancy, although babies born to women on HAART were more likely (26.3%) to have low birth weight than babies born to women who received scARV (12.4%). Also, 7.5% of women on HAART developed side effects requiring a change in their medications. Combining the results from HAART and scART groups, the chance of HIV transmission around the time of birth was 2.2%, increasing to 5.7% at age 1 y. (Three-quarters of the infants were breast-fed; safe water for mixing formula was not reliably available.) The study found no difference in risk of HIV infection between babies whose mothers received HAART and those whose mothers received scARV according to guidelines.
What Do These Findings Mean?
These results support the safety and effectiveness of the WHO two-tiered approach for preventing mother-to-child transmission. This study was not designed to compare HAART to scART directly, because the women who received HAART were the ones with more advanced HIV infection, which might have affected their babies in many ways.
Compared to earlier pregnancy studies of HAART in rich countries, this study of the WHO approach in West Africa showed similar success in protecting infants from HIV infection around the time of birth. Unfortunately, because formula feeding was not generally available in resource-limited settings, protection declined over the first year of life with breast-feeding, but some protection remained.
This study confirms that close monitoring of pregnant women on HAART is necessary, so that drugs can be changed if side effects develop. The study does not tell us whether using scARV in pregnancy might change the virus in ways that would make it more difficult to treat the same women with HAART later if they needed it. The reason for low birth weight in some babies born to mothers on HAART is unclear. It may be because the women who needed HAART had more severe health problems from their HIV, or it may be a result of the HAART itself.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040257.
World Health Organization has a page on prevention of mother-to-child transmission of HIV
"Women, Children, and HIV" is a resource site from the François Xavier Bagnoud Center and UCSF
The MTCT-Plus initiative at Columbia University supports the programs in Abidjan
Related Articles
Current Challenges to the United States' AIDS Drug Assistance Program and Possible Implications of the Affordable Care Act
McManus, Kathleen A.
Engelhard, Carolyn L.
Dillingham, Rebecca
AIDS Research and Treatment
AIDS Drug Assistance Programs, enacted through the Ryan White Comprehensive AIDS Resources Emergency Act of 1990, are the "payer of last resort" for prescription medications for lower income, uninsured, or underinsured people living with HIV/AIDS. ADAPs face declining funding from the federal government. State funding of ADAP is discretionary, but some states increased their contributions to meet the gap in funding. The demand for ADAP support is increasing as people living with HIV are living longer; the antiretroviral therapy (ART) guidelines have been changed to recommend initiation of treatment for all; the United States is increasing HIV testing goals; and the recession continues. In the setting of increased demand and limited funding, ADAPs are employing cost containment measures. Since 2010, emergency federal funds have bailed out ADAP, but these are not sustainable. In the coming years, providers and policy makers associated with HIV care will need to navigate the implementation of the Affordable Care Act (ACA). Lessons learned from the challenges associated with providing sustainable access to ART for vulnerable populations through ADAP should inform upcoming decisions about how to ensure delivery of ART during and after the implementation of the ACA.
Related Articles
Is the US AIDS Drug Assistance Program Cost-effective?
Pinkerton, Steven D.
Kibicho, Jennifer W.
Galletly, Carol L.
AIDS and behavior
Each year, the US AIDS Drug Assistance Program provides access to prescription drugs—including antiretrovirals—to more than 110,000 persons living with HIV (PLWH) who lack adequate medical insurance. PLWH on effective antiretroviral therapy live longer lives, with enhanced quality of life, and are less likely to transmit HIV to others. There are thus significant benefits associated with the ADAP program. But there also are substantial costs. A mathematical model was used to assess the cost-effectiveness of the US ADAP program. Findings indicate that by providing antiretrovirals to underinsured persons, the ADAP program prevented 3191 secondary infections and saved 24,922 quality-adjusted life years in 2008. The net cost per quality-adjusted life year saved was $11,955, which suggests that the ADAP program is cost-effective by conventional standards.
AIDS Drug Assistance Program; antiretroviral therapy; cost-effectiveness
Related Articles
Association between U.S. State AIDS Drug Assistance Program (ADAP) Features and HIV Antiretroviral Therapy Initiation, 2001–2009
Hanna, David B.
Buchacz, Kate
Gebo, Kelly A.
Hessol, Nancy A.
Horberg, Michael A.
Jacobson, Lisa P.
Kirk, Gregory D.
Kitahata, Mari M.
Korthuis, P. Todd
Moore, Richard D.
Napravnik, Sonia
Patel, Pragna
Silverberg, Michael J.
Sterling, Timothy R.
Willig, James H.
Collier, Ann
Samji, Hasina
Thorne, Jennifer E.
Althoff, Keri N.
Martin, Jeffrey N.
Rodriguez, Benigno
Stuart, Elizabeth A.
Gange, Stephen J.
PLoS ONE
U.S. state AIDS Drug Assistance Programs (ADAPs) are federally funded to provide antiretroviral therapy (ART) as the payer of last resort to eligible persons with HIV infection. States differ regarding their financial contributions to and ways of implementing these programs, and it remains unclear how this interstate variability affects HIV treatment outcomes.
We analyzed data from HIV-infected individuals who were clinically-eligible for ART between 2001 and 2009 (i.e., a first reported CD4+ <350 cells/uL or AIDS-defining illness) from 14 U.S. cohorts of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). Using propensity score matching and Cox regression, we assessed ART initiation (within 6 months following eligibility) and virologic suppression (within 1 year) based on differences in two state ADAP features: the amount of state funding in annual ADAP budgets and the implementation of waiting lists. We performed an a priori subgroup analysis in persons with a history of injection drug use (IDU).
Among 8,874 persons, 56% initiated ART within six months following eligibility. Persons living in states with no additional state contribution to the ADAP budget initiated ART on a less timely basis (hazard ratio [HR] 0.73, 95% CI 0.60–0.88). Living in a state with an ADAP waiting list was not associated with less timely initiation (HR 1.12, 95% CI 0.87–1.45). Neither additional state contributions nor waiting lists were significantly associated with virologic suppression. Persons with an IDU history initiated ART on a less timely basis (HR 0.67, 95% CI 0.47–0.95).
We found that living in states that did not contribute additionally to the ADAP budget was associated with delayed ART initiation when treatment was clinically indicated. Given the changing healthcare environment, continued assessment of the role of ADAPs and their features that facilitate prompt treatment is needed.
Related Articles
Effects of recent Virginia AIDS Drug Assistance Program policy changes on diabetes and hyperlipidemia control in people living with HIV
McManus, Kathleen A
Pinkerton, Relana
Dillingham, Rebecca
SAGE open medicine
To describe the impacts of Virginia AIDS Drug Assistance Program's elimination of diabetes and hyperlipidemia medication on disease outcomes in people living with HIV.
Data were collected on two groups of people living with HIV who were prescribed medications for diabetes and/or hyperlipidemia; one group received medications from AIDS Drug Assistance Program (ADAP) and the other group received medications from another source. Data were collected for 13 months before and after the policy change. Diabetes, hyperlipidemia, and HIV control were compared using standard laboratory measures.
During the pre-policy-change time period, non-ADAP patients had better diabetes control than ADAP patients, but with multivariate analysis, ADAP status was no longer a statistically significant predictor. Otherwise, no significant differences between groups were identified.
ADAP patients had worse diabetes control compared to the non-ADAP group before the policy change. It is possible that this is due to the AIDS Drug Assistance Program population's poor access to non-HIV primary care, including care for diabetes. It is reassuring that, even during a time of flux in AIDS Drug Assistance Program resources, the AIDS Drug Assistance Program patients' co-morbid and HIV outcomes were not negatively impacted.
HIV; AIDS Drug Assistance Program; ADAP; diabetes mellitus; hyperlipidemia; AIDS; health policy change
Related Articles
Underutilization of the AIDS Drug Assistance Program: Associated Factors and Policy Implications
Godwin, Noah C
Willig, James H
Nevin, Christa R
Lin, Hui-Yi
Allison, Jeroan
Gaddis, Kathy
Peterson, Jennifer
Saag, Michael S
Mugavero, Michael J
Raper, James L
Health Services Research
The AIDS Drug Assistance Program (ADAP) provides antiretroviral medications to low-income individuals with HIV infection.
A prospective cohort study of ADAP utilization, measured using medication possession ratio (MPR), was conducted during the 2008 calendar year at the University of Alabama at Birmingham 1917 HIV Clinic. Multivariable ordinal logistic regression evaluated factors associated with ADAP utilization.
Among 245 patients, MPR quartiles (Q) were the following: Q1<69 percent, Q2 = 69–83 percent, Q3 = 84–93 percent, Q4>93 percent. In ordinal logistic regression, younger age (OR = 0.59 per 10 years; 95 percent CI = 0.44–0.79), nonwhite males (2.18; 1.18–4.04), lower CD4 count (2.79 for <200 cells/mm3; 1.44–5.43), and a history of alcohol abuse (2.11; 1.02–4.37) were associated with poor ADAP utilization.
One quarter of ADAP enrollees had MPR below 69 percent, a level well below that associated with optimal HIV treatment outcomes, indicating a need for programmatic interventions to improve ADAP utilization.
HIV; adherence; public health
Related Articles
The Impact of HAART on the Respiratory Complications of HIV Infection: Longitudinal Trends in the MACS and WIHS Cohorts
Gingo, Matthew R.
Balasubramani, G. K.
Kingsley, Lawrence
Rinaldo, Charles R.
Alden, Christine B.
Detels, Roger
Greenblatt, Ruth M.
Hessol, Nancy A.
Holman, Susan
Huang, Laurence
Kleerup, Eric C.
Phair, John
Sutton, Sarah H.
Seaberg, Eric C.
Margolick, Joseph B.
Wisniewski, Stephen R.
Morris, Alison
PLoS ONE
To review the incidence of respiratory conditions and their effect on mortality in HIV-infected and uninfected individuals prior to and during the era of highly active antiretroviral therapy (HAART).
Two large observational cohorts of HIV-infected and HIV-uninfected men (Multicenter AIDS Cohort Study [MACS]) and women (Women's Interagency HIV Study [WIHS]), followed since 1984 and 1994, respectively.
Adjusted odds or hazards ratios for incident respiratory infections or non-infectious respiratory diagnoses, respectively, in HIV-infected compared to HIV-uninfected individuals in both the pre-HAART (MACS only) and HAART eras; and adjusted Cox proportional hazard ratios for mortality in HIV-infected persons with lung disease during the HAART era.
Compared to HIV-uninfected participants, HIV-infected individuals had more incident respiratory infections both pre-HAART (MACS, odds ratio [adjusted-OR], 2.4; 95% confidence interval [CI], 2.2–2.7; p<0.001) and after HAART availability (MACS, adjusted-OR, 1.5; 95%CI 1.3–1.7; p<0.001; WIHS adjusted-OR, 2.2; 95%CI 1.8–2.7; p<0.001). Chronic obstructive pulmonary disease was more common in MACS HIV-infected vs. HIV-uninfected participants pre-HAART (hazard ratio [adjusted-HR] 2.9; 95%CI, 1.02–8.4; p = 0.046). After HAART availability, non-infectious lung diseases were not significantly more common in HIV-infected participants in either MACS or WIHS participants. HIV-infected participants in the HAART era with respiratory infections had an increased risk of death compared to those without infections (MACS adjusted-HR, 1.5; 95%CI, 1.3–1.7; p<0.001; WIHS adjusted-HR, 1.9; 95%CI, 1.5–2.4; p<0.001).
HIV infection remained a significant risk for infectious respiratory diseases after the introduction of HAART, and infectious respiratory diseases were associated with an increased risk of mortality.
Related Articles
Emergence of Drug Resistance Is Associated with an Increased Risk of Death among Patients First Starting HAART
Hogg, Robert S
Bangsberg, David R
Lima, Viviane D
Alexander, Chris
Bonner, Simon
Yip, Benita
Wood, Evan
Dong, Winnie W. Y
Montaner, Julio S. G
Harrigan, P. Richard
PLoS Medicine
The impact of the emergence of drug-resistance mutations on mortality is not well characterized in antiretroviral-naïve patients first starting highly active antiretroviral therapy (HAART). Patients may be able to sustain immunologic function with resistant virus, and there is limited evidence that reduced sensitivity to antiretrovirals leads to rapid disease progression or death. We undertook the present analysis to characterize the determinants of mortality in a prospective cohort study with a median of nearly 5 y of follow-up. The objective of this study was to determine the impact of the emergence of drug-resistance mutations on survival among persons initiating HAART.
Methods and Findings
Participants were antiretroviral therapy naïve at entry and initiated triple combination antiretroviral therapy between August 1, 1996, and September 30, 1999. Marginal structural modeling was used to address potential confounding between time-dependent variables in the Cox proportional hazard regression models. In this analysis resistance to any class of drug was considered as a binary time-dependent exposure to the risk of death, controlling for the effect of other time-dependent confounders. We also considered each separate class of mutation as a binary time-dependent exposure, while controlling for the presence/absence of other mutations. A total of 207 deaths were identified among 1,138 participants over the follow-up period, with an all cause mortality rate of 18.2%. Among the 679 patients with HIV-drug-resistance genotyping done before initiating HAART, HIV-drug resistance to any class was observed in 53 (7.8%) of the patients. During follow-up, HIV-drug resistance to any class was observed in 302 (26.5%) participants. Emergence of any resistance was associated with mortality (hazard ratio: 1.75 [95% confidence interval: 1.27, 2.43]). When we considered each class of resistance separately, persons who exhibited resistance to non-nucleoside reverse transcriptase inhibitors had the highest risk: mortality rates were 3.02 times higher (95% confidence interval: 1.99, 4.57) for these patients than for those who did not exhibit this type of resistance.
We demonstrated that emergence of resistance to non-nucleoside reverse transcriptase inhibitors was associated with a greater risk of subsequent death than was emergence of protease inhibitor resistance. Future research is needed to identify the particular subpopulations of men and women at greatest risk and to elucidate the impact of resistance over a longer follow-up period.
Emergence of resistance to both non-nucleoside reverse transcriptase inhibitors and protease inhibitors was associated with a higher risk of subsequent death, but the risk was greater in patients with NNRTI-resistant HIV.
Editors' Summary
In the 1980s, infection with the human immunodeficiency virus (HIV) was effectively a death sentence. HIV causes AIDS (acquired immunodeficiency syndrome) by replicating inside immune system cells and destroying them, which leaves infected individuals unable to fight off other viruses and bacteria. The first antiretroviral drugs were developed quickly, but it soon became clear that single antiretrovirals only transiently suppress HIV infection. HIV mutates (accumulates random changes to its genetic material) very rapidly and, although most of these changes (or mutations) are bad for the virus, by chance some make it drug resistant. Highly active antiretroviral therapy (HAART), which was introduced in the mid-1990s, combines three or four antiretroviral drugs that act at different stages of the viral life cycle. For example, they inhibit the reverse transcriptase that the virus uses to replicate its genetic material, or the protease that is necessary to assemble new viruses. With HAART, the replication of any virus that develops resistance to one drug is inhibited by the other drugs in the mix. As a consequence, for many individuals with access to HAART, AIDS has become a chronic rather than a fatal disease. However, being on HAART requires patients to take several pills a day at specific times. In addition, the drugs in the HAART regimens often have side effects.
Why Was This Study Done?
Drug resistance still develops even with HAART, often because patients don't stick to the complicated regimens. The detection of resistance to one drug is usually the prompt to change a patient's drug regimen to head off possible treatment failure. Although most patients treated with HAART live for many years, some still die from AIDS. We don't know much about how the emergence of drug-resistance mutations affects mortality in patients who are starting antiretroviral therapy for the first time. In this study, the researchers looked at how the emergence of drug resistance affected survival in a group of HIV/AIDS patients in British Columbia, Canada. Here, everyone with HIV/AIDS has access to free medical attention, HAART, and laboratory monitoring, and full details of all HAART recipients are entered into a central reporting system.
What Did the Researchers Do and Find?
The researchers enrolled people who started antiretroviral therapy for the first time between August 1996 and September 1999 into the HAART Observational Medical Evaluation and Research (HOMER) cohort. They then excluded anyone who was infected with already drug-resistant HIV strains (based on the presence of drug-resistance mutations in viruses isolated from the patients) at the start of therapy. The remaining 1,138 patients were followed for an average of five years. All the patients received either two nucleoside reverse transcriptase inhibitors and a protease inhibitor, or two nucleoside and one non-nucleoside reverse transcriptase inhibitor (NNRTI). Nearly a fifth of the study participants died during the follow-up period. Most of these patients actually had drug-sensitive viruses, possibly because they had neglected taking their drugs to such an extent that there had been insufficient drug exposure to select for drug-resistant viruses. In a quarter of the patients, however, HIV strains resistant to one or more antiretroviral drugs emerged during the study (again judged by looking for mutations). Detailed statistical analyses indicated that the emergence of any drug resistance nearly doubled the risk of patients dying, and that people carrying viruses resistant to NNRTIs were three times as likely to die as those without resistance to this class of antiretroviral drug.
What Do These Findings Mean?
These results provide new information about the emergence of drug-resistant HIV during HAART and possible effects on the long-term survival of patients. In particular, they suggest that clinicians should watch carefully for the emergence of resistance to NNRTIs in their patients. Because this type of resistance is often due to poor adherence to drug regimens, these results also suggest that increased efforts should be made to ensure that patients comply with the prescribed HAART regimens, especially those whose antiretroviral therapy includes NNRTIs. As with all studies in which a group of individuals who share a common characteristic are studied over time, it is possible that some other, unmeasured difference between the patients who died and those who didn't—rather than emerging drug resistance—is responsible for the observed differences in survival. Additional studies are needed to confirm the findings here, and to investigate whether specific subpopulations of patients are at particular risk of developing drug resistance and/or dying during HAART.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030356.
US National Institute of Allergy and Infectious Diseases fact sheet on HIV infection and AIDS
US Department of Health and Human Services information on AIDS, including details of approved drugs for the treatment of HIV infection
US Centers for Disease Control and Prevention information on HIV/AIDS
Aidsmap, information on HIV and AIDS provided by the charity NAM, which includes details on antiretroviral drugs
Related Articles
The Effect of Highly Active Antiretroviral Therapy on the Survival of HIV-Infected Children in a Resource-Deprived Setting: A Cohort Study
Edmonds, Andrew
Yotebieng, Marcel
Lusiama, Jean
Matumona, Yori
Kitetele, Faustin
Napravnik, Sonia
Cole, Stephen R.
Van Rie, Annelies
Behets, Frieda
PLoS Medicine
This observational cohort study by Andrew Edmonds and colleagues reports that treatment with highly active antiretroviral therapy (HAART) markedly improves the survival of HIV-infected children in Kinshasa, DRC, a resource-deprived setting.
The effect of highly active antiretroviral therapy (HAART) on the survival of HIV-infected children has not been well quantified. Because most pediatric HIV occurs in low- and middle-income countries, our objective was to provide a first estimate of this effect among children living in a resource-deprived setting.
Methods and Findings
Observational data from HAART-naïve children enrolled into an HIV care and treatment program in Kinshasa, Democratic Republic of the Congo, between December 2004 and May 2010 were analyzed. We used marginal structural models to estimate the effect of HAART on survival while accounting for time-dependent confounders affected by exposure. At the start of follow-up, the median age of the 790 children was 5.9 y, 528 (66.8%) had advanced or severe immunodeficiency, and 405 (51.3%) were in HIV clinical stage 3 or 4. The children were observed for a median of 31.2 mo and contributed a total of 2,089.8 person-years. Eighty children (10.1%) died, 619 (78.4%) initiated HAART, six (0.8%) transferred to a different care provider, and 76 (9.6%) were lost to follow-up. The mortality rate was 3.2 deaths per 100 person-years (95% confidence interval [CI] 2.4–4.2) during receipt of HAART and 6.0 deaths per 100 person-years (95% CI 4.1–8.6) during receipt of primary HIV care only. The mortality hazard ratio comparing HAART with no HAART from a marginal structural model was 0.25 (95% CI 0.06–0.95).
HAART reduced the hazard of mortality in HIV-infected children in Kinshasa by 75%, an estimate that is similar in magnitude but with lower precision than the reported effect of HAART on survival among children in the United States.
Please see later in the article for the Editors' Summary
Editors' Summary
In 2009, an estimated 2.5 million children were living with HIV, the majority of whom (2.3 million) were in sub-Saharan Africa. Most (90%) of these children acquired HIV from their HIV-infected mothers during pregnancy, birth, or breastfeeding, highlighting the importance of giving effective drugs for the prevention of mother to child transmission. As such interventions are still not widely accessible or available in most resource-limited countries, where the burden of HIV is highest, every day an estimated 1,000 children were newly infected with HIV in 2009, but only 360,000 children were receiving highly active antiretroviral therapy (HAART).
Although HAART improves the survival of adults living with HIV, less is known about the degree to which HAART affects the survival of HIV-infected children—although response to antiretroviral treatment is known to differ across age groups. Furthermore, as the course of HIV disease in children is different from that in adults (partly because of the impact of the virus on the immature thymus, which can lead to high HIV RNA viremia and rapid death), it is inappropriate to extrapolate results from studies of adults to pediatric populations. Therefore, it is imperative that the effect of HAART on survival be quantified specifically in children.
Why Was This Study Done?
Most observational studies of the effects of treatment on child survival have been undertaken in high-income countries, such as Italy and the United States. As most children with HIV live in low-resource areas, where multiple factors, such as delayed presentation to care and a higher incidence of co-occurring conditions, might adversely affect treatment outcomes, there is a specific need for information on the effects of HAART in children with HIV living in low-income countries. Although some investigations have taken place in pediatric cohorts from such countries (for example, Côte d'Ivoire, Haiti, Lesotho, Thailand, and Zambia), the effect of HAART on mortality has not been accurately quantified among children in a resource-deprived setting. Therefore, in this observational clinical cohort study, the researchers investigated the effect of HAART on mortality in HIV-infected children in Kinshasa, in the Democratic Republic of the Congo (DRC).
What Did the Researchers Do and Find?
The researchers analyzed data from 790 children enrolled into an HIV program in Kinshasa, DRC, between December 2004 and May 2010 and used a statistical model (marginal structural models) to adjust for time-dependent confounding factors, such as the fact that HAART is typically initiated in sicker patients, for example, those with lower CD4 cell percentages. Assuming that all children starting HAART received it uninterruptedly throughout follow-up, using this statistical model, the researchers were able to compare the hazard ratio of death had all children initiated HAART to that had no children initiated HAART during follow-up.
In the study, 619 out of the 790 children (78.4%) initiated HAART during follow-up and were followed for a median of 31.2 months, with a median of 30 HIV care visits. Of those who started treatment, 110 (17.8%) switched to an alternative regimen because of an adverse event or treatment failure. During the 2,089.8 accrued person-years of follow-up, 80 children (10.1%) died, giving an overall mortality rate of 3.8 deaths per 100 person-years. The unadjusted mortality rate ratio comparing HAART to no HAART was 0.54. Using a marginal structural model, the researchers estimated that compared to no HAART, HAART reduced the hazard (rate) of mortality during follow-up by 75%.
What Do These Findings Mean?
These findings show that treatment with HAART markedly improved the survival of children infected with HIV in Kinshasa, DRC, and suggest that HAART is as effective in improving the survival of HIV-infected children in a severely resource-deprived country (still recovering from civil war) as in more resource-privileged settings—an important finding given that the vast majority of children receiving HAART live in resource-poor areas. This study provides additional evidence that accelerating rollout of antiretroviral therapy to children with HIV in resource-poor countries is lifesaving and effective. Future research needs to address how effective HAART is in understudied populations in resource-poor countries, such as undernourished children or those with co-infections such as tuberculosis.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001044.
The World Health Organization's Web site has more information about the treatment of children living with HIV
Médecins Sans Frontières's Campaign for Access to Essential Medicines Web site has more information on pediatric HAART
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Integrating Substance Abuse Treatment into HIV Care: Missed Opportunities in the AIDS Drug Assistance Program
Martin, Erika G.
Wang, Karen H.
Journal of acquired immune deficiency syndromes (1999)
Untreated substance use disorders (SUD) among HIV patients contribute to worse HIV care outcomes and increased HIV transmission. Although there are clinical and policy recommendations for integrated SUD and HIV treatment, payment issues including complex funding streams are a barrier.
We assessed the availability of guideline-concordant medication-assisted therapies to treat alcohol, tobacco, and opioid dependence on state-administered AIDS Drug Assistance Programs (ADAPs), an important source of drug coverage for low-income HIV patients. We examined which medication-assisted therapies are most likely to be included on formularies, and variation of these therapies across states.
Research Design
We reviewed state-specific ADAP formularies from 1997 to 2009 for the presence of guideline-concordant medication-assisted therapies to treat alcohol, tobacco, and opioid dependence.
The most frequently included medication-assisted therapies were those to treat tobacco dependence, followed by opioid dependence. Few states covered alcohol dependence medications. In each year, <10% of states covered all recommended medications and <50% covered a partial formulary for at least one SUD.
ADAPs could provide access to medication-assisted therapies for SUD for a significant number of HIV patients, but these medications have not been widely covered throughout the program's history. Increased availability of medication-assisted therapies through ADAP could facilitate integrated HIV and SUD care.
Ryan White HIV/AIDS Program; substance use disorders; HIV/AIDS; coverage; health policy
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Improving Outcomes in State AIDS Drug Assistance Programs
Linas, Benjamin P.
Losina, Elena
Rockwell, Annette
Walensky, Rochelle P.
Cranston, Kevin
Freedberg, Kenneth A.
Journal of acquired immune deficiency syndromes (1999)
State AIDS Drug Assistance Programs (ADAPs) provide antiretroviral medications to patients with no access to medications. Resource constraints limit many ADAPs' ability to meet demand for services.
To determine ADAP eligibility criteria that minimize morbidity and mortality and contain costs.
We used Discrete Event Simulation to model the progression of HIV-infected patients and track utilization of an ADAP. Outcomes included five-year mortality and incidence of first opportunistic infection or death, and time to starting ART. We compared expected outcomes for two policies: 1) first-come, first-served (FCFS) eligibility for all with CD4 count ≤350/μl (current standard), and 2) CD4 count prioritized eligibility for those with CD4 counts below a defined threshold.
In the base case, prioritizing patients with CD4 counts ≤250/μl led to lower five-year mortality than FCFS eligibility [2.77 vs. 3.27 deaths/1,000 person months], and to a lower incidence of first opportunistic infection or death [5.55 vs. 6.98 events/1,000 person months]. CD4-based eligibility reduced the time to starting ART for patients with CD4 counts ≤200/μl. In sensitivity analyses, CD4-based eligibility consistently led to lower morbidity and mortality than FCFS eligibility.
When resources are limited, programs that provide ART can improve outcomes by prioritizing patients with low CD4 counts.
AIDS; Anti-HIV Agents*/therapeutic use; ADAP; Government Programs; Resource Allocation*; CD4 Lymphocyte Count
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Public-Health and Individual Approaches to Antiretroviral Therapy: Township South Africa and Switzerland Compared
Keiser, Olivia
Orrell, Catherine
Egger, Matthias
Wood, Robin
Brinkhof, Martin W. G
Furrer, Hansjakob
van Cutsem, Gilles
Ledergerber, Bruno
Boulle, Andrew
PLoS Medicine
The provision of highly active antiretroviral therapy (HAART) in resource-limited settings follows a public health approach, which is characterised by a limited number of regimens and the standardisation of clinical and laboratory monitoring. In industrialized countries doctors prescribe from the full range of available antiretroviral drugs, supported by resistance testing and frequent laboratory monitoring. We compared virologic response, changes to first-line regimens, and mortality in HIV-infected patients starting HAART in South Africa and Switzerland.
Methods and Findings
We analysed data from the Swiss HIV Cohort Study and two HAART programmes in townships of Cape Town, South Africa. We included treatment-naïve patients aged 16 y or older who had started treatment with at least three drugs since 2001, and excluded intravenous drug users. Data from a total of 2,348 patients from South Africa and 1,016 patients from the Swiss HIV Cohort Study were analysed. Median baseline CD4+ T cell counts were 80 cells/μl in South Africa and 204 cells/μl in Switzerland. In South Africa, patients started with one of four first-line regimens, which was subsequently changed in 514 patients (22%). In Switzerland, 36 first-line regimens were used initially, and these were changed in 539 patients (53%). In most patients HIV-1 RNA was suppressed to 500 copies/ml or less within one year: 96% (95% confidence interval [CI] 95%–97%) in South Africa and 96% (94%–97%) in Switzerland, and 26% (22%–29%) and 27% (24%–31%), respectively, developed viral rebound within two years. Mortality was higher in South Africa than in Switzerland during the first months of HAART: adjusted hazard ratios were 5.90 (95% CI 1.81–19.2) during months 1–3 and 1.77 (0.90–3.50) during months 4–24.
Compared to the highly individualised approach in Switzerland, programmatic HAART in South Africa resulted in similar virologic outcomes, with relatively few changes to initial regimens. Further innovation and resources are required in South Africa to both achieve more timely access to HAART and improve the prognosis of patients who start HAART with advanced disease.
Comparing HIV treatment in Switzerland, where drug selection is individualized, and South Africa, where a programmatic approach is used, Matthias Egger and colleagues find similar virologic outcomes over two years.
Editors' Summary
Acquired immunodeficiency syndrome (AIDS) has killed more than 25 million people since the first reported case in 1981, and more than 30 million people are now infected with the human immunodeficiency virus (HIV), which causes AIDS. HIV destroys immune system cells (including CD4 cells, a type of lymphocyte), leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, most HIV-infected people died within 10 years of becoming infected. Then, in 1996, highly active antiretroviral therapy (HAART)—a combination of several antiretroviral drugs—was developed. Now, in resource-rich countries, clinicians provide individually tailored care for HIV-infected people by prescribing combinations of antiretroviral drugs chosen from more than 20 approved medicines. The approach to treatment of HIV in developed countries typically also includes frequent monitoring of the amount of virus in patients' blood (viral load), viral resistance testing (to see whether any viruses are resistant to specific antiretroviral drugs), and regular CD4 cell counts (an indication of immune-system health). Since the implementation of these interventions, the health and life expectancy of people with HIV has improved dramatically in these countries.
Why Was This Study Done?
The history of HIV care in resource-poor countries has been very different. Initially, these countries could not afford to provide HAART for their populations. In 2003, however, governments, international agencies, and funding bodies began to implement plans to increase HAART coverage in developing countries. By December 2006, more than a quarter of the HIV-infected people in low- and middle-income countries who urgently needed treatment were receiving HAART. However, instead of individualized treatment, HAART programs in developing countries follow a public-health approach developed by the World Health Organization. That is, drug regimens, clinical decision-making, and clinical and laboratory monitoring are all standardized. This public-health approach takes into account the realities of under-resourced health systems, but is it as effective as the individualized approach? The researchers addressed this question by comparing virologic responses (the effect of treatment on the viral load), changes to first-line (initial) therapy, and deaths in patients receiving HAART in South Africa (public-health approach) and in Switzerland (individualized approach).
What Did the Researchers Do and Find?
The researchers analyzed data collected since 2001 from more than 2,000 patients enrolled in HAART programs in two townships (Gugulethu and Khayelitsha) in Cape Town, South Africa, and from more than 1,000 patients enrolled in the Swiss HIV Cohort Study, a nationwide study of HIV-infected people. The patients in South Africa, who had a lower starting CD4 cell count and were more likely to have advanced AIDS than the patients in Switzerland, started their treatment for HIV infection with one of four first-line therapies, and about a quarter changed to a second-line therapy during the study. By contrast, 36 first-line regimens were used in Switzerland and half the patients changed to a different regimen. Despite these differences, the viral load was greatly reduced within a year in virtually all the patients and viral rebound (an increased viral load after a low measurement) developed within 2 years in a quarter of the patients in both countries. However, more patients died in South Africa than in Switzerland, particularly during the first 3 months of therapy.
What Do These Findings Mean?
These findings suggest that the public-health approach to HAART practiced in South Africa is as effective in terms of virologic outcomes as the individualized approach practiced in Switzerland. This is reassuring because it suggests that "antiretroviral anarchy" (the unregulated use of antiretroviral drugs, interruptions in drug supplies, and the lack of treatment monitoring), which is likely to lead to the emergence of viral resistance, is not happening in South Africa as some experts feared it might. Thus, these findings support the continued rollout of the public-health approach to HAART in resource-poor countries. Conversely, they also suggest that a more standardized approach to HAART could be taken in Switzerland (and in other industrialized countries) without compromising its effectiveness. Finally, the higher mortality in South Africa than in Switzerland, which partly reflects the many patients in South Africa in desperate need of HAART and their more advanced disease at the start of therapy, suggests that HIV-infected patients in South Africa and in other resource-limited countries would benefit from earlier initiation of therapy.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050148.
The World Health Organization provides information about universal access to HIV treatment (in several languages) and on its recommendations for a public-health approach to antiretroviral therapy for HIV infection
More details on the Swiss HIV Cohort Study and on the studies in Gugulethu and Khayelitsha are available
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
HIV InSite has comprehensive information on all aspects of HIV/AIDS, including detailed information about antiretroviral therapy and links to treatment guidelines for various countries
Information is available from Avert, an international AIDS charity, on HIV and AIDS around the world and on providing AIDS drug treatment for millions
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Assessing the effect of HAART on change in quality of life among HIV-infected women
Liu, Chenglong
Weber, Kathleen
Robison, Esther
Hu, Zheng
Jacobson, Lisa P
Gange, Stephen J
AIDS Research and Therapy
The impact of highly active antiretroviral therapy (HAART) on health-related quality of life (QOL) of HIV-1 infected individuals in large prospective cohorts has not been well studied.
To assess the effect of HAART on QOL by comparing HIV-infected women using HAART with HIV-infected women remaining HAART naïve in the Women's Interagency HIV Study (WIHS), a multicenter prospective cohort study begun in 1994 in the US.
A 1:1 matching with equivalent (≤ 0.1%) propensity scores for predicting HAART initiation was implemented and 458 pairs were obtained. HAART effects were assessed using pattern mixture models. The changes of nine QOL domain scores and one summary score derived from a shortened version of the MOS-HIV from initial values were used as study outcomes.
The background covariates of the treatment groups were well-balanced after propensity score matching. The 916 matched subjects had a mean age of 38.5 years and 42% had a history of AIDS diagnosis. The participants contributed a total of 4,292 person visits with a median follow-up time of 4 years. In the bivariate analyses with only HAART use and time as covariates, HAART was associated with short-term improvements of 4 QOL domains: role functioning, social functioning, pain and perceived health index. After adjusting for demographic, socioeconomic, biological and clinical variables, HAART had small but significant short-term improvements on changes in summary QOL (mean change: 3.25; P = 0.02), role functioning (6.99; P < 0.01), social functioning (5.74; P < 0.01), cognitive functioning (3.59; P = 0.03), pain (6.73; P < 0.01), health perception (3.67; P = 0.03) and perceived health index (4.87; P < 0.01). These QOL scores typically remained stable or declined over additional follow-up and there was no indication that HAART modified these trends.
Our study demonstrated significant short-term HAART effects on most QOL domains, but additional use of HAART did not modify long-term trends. These changes could be attributed to the direct effect of HAART and indirect HAART effect mediated through clinical changes.
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Association of Race, Substance Abuse, and Health Insurance Coverage With Use of Highly Active Antiretroviral Therapy Among HIV-Infected Women, 2005
Lillie-Blanton, Marsha
Stone, Valerie E.
Jones, Alison Snow
Levi, Jeffrey
Golub, Elizabeth T.
Cohen, Mardge H.
Hessol, Nancy A.
Wilson, Tracey E.
American journal of public health
We examined racial/ethnic disparities in highly active antiretroviral therapy (HAART) use and whether differences are moderated by substance use or insurance status, using data from the Women's Interagency HIV Study (WIHS).
Logistic regression examined HAART use in a longitudinal cohort of women for whom HAART was clinically indicated in 2005 (N=1354).
Approximately 3 of every 10 eligible women reported not taking HAART. African American and Hispanic women were less likely than were White women to use HAART. After we adjusted for potential confounders, the higher likelihood of not using HAART persisted for African American but not for Hispanic women. Uninsured and privately insured women, regardless of race/ethnicity, were less likely than were Medicaid enrollees to use HAART. Although alcohol use was related to HAART nonuse, illicit drug use was not.
These findings suggest that expanding and improving insurance coverage should increase access to antiretroviral therapy across racial/ethnic groups, but it is not likely to eliminate the disparity in use of HAART between African American and White women with HIV/AIDS.
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Using cost as a consideration for antiretroviral regimen selection: an example using average wholesale prices
Grimes, Richard M.
Shenouda, Tina A.
AIDS care
Funding for the AIDS Drug Assistance Program (ADAP) has lagged behind the number of persons needing antiretroviral therapy, leading to waiting lists and reduction of needed treatments and services. This paper demonstrates a method of providing more treatment for the same amount of money by selecting clinically equivalent, but lower cost drug regimens. Average wholesale prices (AWPs) were used to calculate the annual costs of preferred, alternative and acceptable regimens. The cost of each regimen was divided into $1,000,000 to determine how many patients could be treated per $1,000,000 that an ADAP had to spend. AWPs for preferred regimens ranged from $25,318 to 35,645 per year. For alternative regimens, the range of annual AWPs was $22,002 to $32,335. The range for the acceptable regimens was $19,031 to $31,543. The range of person treated/$1,000,000 per year was from 28 to 52. Funding shortages will lead ADAPs to resort to waiting lists or other means of denying appropriate care unless alternative approaches to treatment are sought. Cost conscious selection of regimens where there is no harm to individual patients is one alternative approach. Medical conditions that allow exceptions to a lower cost based regimens must be developed with the assistance of clinicians.
Cost; Antiretroviral drugs; regimen selection
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Effects of highly active antiretroviral therapy and its adherence on herpes zoster incidence: a longitudinal cohort study
Liu, Chenglong
Wang, Cuiwei
Glesby, Marshall J
D'souza, Gypsyamber
French, Audrey
Minkoff, Howard
Maurer, Toby
Karim, Roksana
Young, Mary
AIDS Research and Therapy
Herpes zoster (HZ) is common among HIV-infected individuals, but the impacts of highly active antiretroviral therapy (HAART) and HAART adherence on HZ risk have not been well studied.
The effects of HAART and HAART adherence on HZ incidence were evaluated by comparing HIV-infected women on HAART (HAART use group) with the HIV-infected women remaining HAART naïve (HAART naïve group) in the Women's Interagency HIV Study (WIHS). A 1:1 matching with propensity score for predicting HAART initiation was conducted to balance background covariates at index visit, including HIV disease stage. Kaplan-Meier method was used to compare the risk of HZ development between the matched pairs. Cox proportional hazard models were used to assess the effects of HAART and HAART adherence on HZ incidence.
Through propensity score matching, 389 pairs of participants were identified and they contributed 3,909 person years after matching. The background covariates were similar between the matched pairs at the index visit. The participants had a mean age around 39 years old, and about 61% of them were Black and 22% were Latina. No significant difference in HZ risk was observed between the HAART use group and the HAART naïve group during the first year of follow-up in any analyses. In the univariate analysis, the HAART use group had marginally lower HZ risk (Hazard Ratio (HR): 0.72; 95% Confidence Interval (CI): 0.48-1.1) over the entire follow-up period. However, women with a HAART adherence level of ≥95% had significantly lower HZ risk (HR: 0.54; 95% CI: 0.31, 0.94) compared to the HAART naïve women. The association remained significant after adjusting for quality of life score and acyclovir use, but it attenuated and was no longer statistically significant after adjusting for an intermediate variable, either CD4+ T cell counts or HIV viral load.
Among adult women, we observed a significant preventive effect of long-term HAART use on HZ incidence when a HAART adherence level of ≥95% was attained, and this effect was mediated through reduction of HIV viral load and improvement of CD4+ T cell counts.
HAART; Adherence; Herpes zoster; Incidence; Propensity score
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Wyatt, Christina M.
Hoover, Donald R.
Shi, Qiuhu
Tien, Phyllis C.
Karim, Roksana
Cohen, Mardge H.
Goderre, Johanna L.
Seaberg, Eric C.
Lazar, Jason
Young, Mary A.
Klotman, Paul E.
Anastos, Kathryn
Antiviral therapy
We previously reported an increased risk of all-cause and AIDS mortality among HIV-infected women with albuminuria (proteinuria or microalbuminuria) enrolled in the Women's Interagency HIV Study (WIHS) prior to the introduction of highly active antiretroviral therapy (HAART).
The current analysis includes 1,073 WIHS participants who subsequently initiated HAART. Urinalysis for proteinuria and semi-quantitative testing for microalbuminuria from two consecutive study visits prior to HAART initiation were categorized as follows: confirmed proteinuria (both specimens positive for protein), confirmed microalbuminuria (both specimens positive with at least one microalbuminuria), unconfirmed albuminuria (one specimen positive for proteinuria or microalbuminuria), or negative (both specimens negative). Time from HAART initiation to death was modeled using proportional hazards analysis.
Compared to the reference group of women with two negative specimens, the hazard ratio (HR) for all-cause mortality was significantly elevated for women with confirmed microalbuminuria (HR 1.9; 95% CI 1.2–2.9). Confirmed microalbuminuria was also independently associated with AIDS death (HR 2.3; 95% CI 1.3–4.3), while women with confirmed proteinuria were at increased risk for non-AIDS death (HR 2.4; 95% CI 1.2–4.6).
In women initiating HAART, pre-existing microalbuminuria independently predicted increased AIDS mortality, while pre-existing proteinuria predicted increased risk of non-AIDS death. Urine testing may identify HIV-infected individuals at increased risk for mortality even after the initiation of HAART. Future studies should consider whether these widely available tests can identify individuals who would benefit from more aggressive management of HIV infection and comorbid conditions associated with mortality in this population.
HIV; microalbuminuria; proteinuria; mortality; non-AIDS death
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An Investigation of the Possible Interaction between the Use of Vitamin C and Highly Active Anti-Retroviral Therapy (HAART) Adherence and Effectiveness in Treated HIV+ Women
Merenstein, Daniel
Wang, Cuiwei
Gandhi, Monica
Robison, Esther
Levine, Alexandra M.
Schwartz, Rebecca M.
Weber, Kathleen M.
Liu, Chenglong
Complementary Therapies in Medicine
Our goal in this study was to examine how Vitamin C interacts with antiretroviral therapy in individuals with HIV. We specifically evaluated how Vitamin C impacts highly active antiretroviral therapy (HAART) adherence and HAART effectiveness as adjudicated by HIV viral loads and CD4 cell counts. Women served as their own controls, comparing periods of Vitamin C usage with periods of non-usage.
An intra-individual, cross-sectional comparative study 'nested' in the WIHS observational cohort study
Women in the Women's Interagency HIV Study (WIHS).
Outcome Measures
Adherence, CD4 count and Viral load.
Our study population was drawn from 2,813 HIV+ participants who contributed 44,588 visits in WIHS from October, 1994 to April, 2009. Among them, there were 1,122 Vitamin C users with 4,954 total visits where use was reported. In the multivariate model adjusting for age, education, race, income, drug use, Vitamin C use order and depression score, there was a 44% increase in the odds of >=95% HAART adherence among participants during their period of Vitamin C use compared to when they were not using Vitamin C (OR=1.44; 95% CI=1.1–1.9; P-value=0.0179). There was an association with Vitamin C usage and CD4 counts on viral loads.
Vitamin C usage appears to be associated with improved adherence. Future Vitamin C studies should target specific HAART drugs, and prospective clinical outcomes.
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Injection drug use and patterns of highly active antiretroviral therapy use: an analysis of ALIVE, WIHS, and MACS cohorts
Morris, John D
Golub, Elizabeth T
Mehta, Shruti H
Jacobson, Lisa P
Gange, Stephen J
AIDS Research and Therapy
Sustained use of antiretroviral therapy has been consistently shown to be one of the primary predictors of long-term effectiveness. Switching and discontinuation reflect patient and provider decisions that may limit future treatment options. In this study, we utilize data reported at semi-annual study visits from three prospective cohort studies, the AIDS Link to IntraVenous Exposure (ALIVE), the Women's Interagency HIV Study (WIHS), and the Multicenter AIDS Cohort Study (MACS), to investigate determinants of HAART modification with a particular focus on reported injection drug use (IDU).
Longitudinal data collected between 1996 and 2004 contributed from 2,266 participants (37% with a reported history of IDU) who reported initiating their first HAART regimen during follow-up were utilized. Separate proportional-hazards models were used to identify factors measured prior to HAART-initiation associated with the time to first HAART discontinuation and first switch of components of HAART among continuous HAART users.
The use of PI- vs. NNRTI-based regimens among HAART users with and without any history of IDU was similar over follow-up. The median time to a first report of discontinuation of HAART was 1.1 years for individuals with a history of IDU but 2.5 years for those without a history of IDU and multivariate analyses confirmed overall that individuals with a history of IDU were at greater risk for HAART discontinuation (adj RH = 1.24, 95% CI: 1.03–1.48). However, when restricting to data contributed after 1999, there was no longer any significant increased risk (adj RH = 1.05, 95% CI: 0.81–1.36). After adjusting for pre-HAART health status and prior ARV exposure, individuals who were ethnic/racial minorities, reported an annual income < $10,000/year, and were not employed were at significantly greater risk for HAART discontinuation. The median time to a first change in HAART regimen was approximately 1.5 years after first HAART report and was not elevated among those with a history of IDU (adj RH = 1.09, 95% CI: 0.89–1.34).
Our analyses demonstrate that injection drug use by itself does not appear to be an independent risk factor for HAART switching or discontinuation in more recent years. However, as continued HAART use is of paramount importance for long-term control of HIV infection, efforts to improve maintenance to therapy among disadvantaged and minority populations remain greatly needed.
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Responding to racial and ethnic disparities in use of HIV drugs: analysis of state policies.
Morin, Stephen F.
Sengupta, Sohini
Cozen, Myrna
Richards, T. Anne
Shriver, Michael D.
Palacio, Herminia
Kahn, James G.
Public Health Reports
OBJECTIVES: The objectives of this study were to assess racial/ethnic trends in surveillance data in four states--California, New York, Florida and Texas, identify structural barriers to and facilitators of access to HIV pharmaceuticals by individuals in Medicaid and the AIDS Drug Assistance Program (ADAP), and identify treatment education and outreach efforts responding to the needs of ethnic minority HIV patients. METHODS: State surveillance and claims data were used to assess trends by race/ethnicity in AIDS cases and mortality as well as participation rates in Medicaid and ADAP. Key informant interviews with state program administrators and local clinic-based benefit eligibility workers were used to identify social and policy barriers to and facilitators of access to HIV drugs and state strategies for overcoming racial/ethnic disparities. RESULTS: Racial/ethnic disparities in the reduction of AIDS-related mortality were identified in three of the four states studied. Policy barriers included Medicaid requirements for legal immigration status and residency, limits on Medicaid eligibility based on disability requirements, and state-imposed income and benefit limits on ADAP. Social barriers to accessing AIDS medications included lack of information, distrust of government, and HIV-related stigma. State strategies for overcoming disparities included contracting with community-based organizations for treatment education and outreach, the use of regional minority coordinators, and public information campaigns. CONCLUSIONS: State policies play a significant role in determining access to HIV drugs, and state policies can be used to reduce racial/ethnic disparities in pharmaceutical access. Overall, eliminating racial/ethnic disparities in access to HIV pharmaceuticals appears to be an achievable goal.
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Switching HIV Treatment in Adults Based on CD4 Count Versus Viral Load Monitoring: A Randomized, Non-Inferiority Trial in Thailand
Jourdain, Gonzague
Le Cœur, Sophie
Ngo-Giang-Huong, Nicole
Traisathit, Patrinee
Cressey, Tim R.
Fregonese, Federica
Leurent, Baptiste
Collins, Intira J.
Techapornroong, Malee
Banchongkit, Sukit
Buranabanjasatean, Sudanee
Halue, Guttiga
Nilmanat, Ampaipith
Luekamlung, Nuananong
Klinbuayaem, Virat
Chutanunta, Apichat
Kantipong, Pacharee
Bowonwatanuwong, Chureeratana
Lertkoonalak, Rittha
Leenasirimakul, Prattana
Tansuphasawasdikul, Somboon
Sang-a-gad, Pensiriwan
Pathipvanich, Panita
Thongbuaban, Srisuda
Wittayapraparat, Pakorn
Eiamsirikit, Naree
Buranawanitchakorn, Yuwadee
Yutthakasemsunt, Naruepon
Winiyakul, Narong
Decker, Luc
Barbier, Sylvaine
Koetsawang, Suporn
Sirirungsi, Wasna
McIntosh, Kenneth
Thanprasertsuk, Sombat
Lallemant, Marc
PLoS Medicine
Using a randomized controlled trial, Marc Lallemant and colleagues ask if a CD4-based monitoring and treatment switching strategy provides a similar clinical outcome compared to the standard viral load-based strategy for adults with HIV in Thailand.
Please see later in the article for the Editors' Summary
Viral load (VL) is recommended for monitoring the response to highly active antiretroviral therapy (HAART) but is not routinely available in most low- and middle-income countries. The purpose of the study was to determine whether a CD4-based monitoring and switching strategy would provide a similar clinical outcome compared to the standard VL-based strategy in Thailand.
Methods and Findings
The Programs for HIV Prevention and Treatment (PHPT-3) non-inferiority randomized clinical trial compared a treatment switching strategy based on CD4-only (CD4) monitoring versus viral-load (VL). Consenting participants were antiretroviral-naïve HIV-infected adults (CD4 count 50–250/mm3) initiating non-nucleotide reverse transcriptase inhibitor (NNRTI)-based therapy. Randomization, stratified by site (21 public hospitals), was performed centrally after enrollment. Clinicians were unaware of the VL values of patients randomized to the CD4 arm. Participants switched to second-line combination with confirmed CD4 decline >30% from peak (within 200 cells from baseline) in the CD4 arm, or confirmed VL >400 copies/ml in the VL arm. Primary endpoint was clinical failure at 3 years, defined as death, new AIDS-defining event, or CD4 <50 cells/mm3. The 3-year Kaplan-Meier cumulative risks of clinical failure were compared for non-inferiority with a margin of 7.4%. In the intent to treat analysis, data were censored at the date of death or at last visit. The secondary endpoints were difference in future-drug-option (FDO) score, a measure of resistance profiles, virologic and immunologic responses, and the safety and tolerance of HAART. 716 participants were randomized, 356 to VL monitoring and 360 to CD4 monitoring. At 3 years, 319 participants (90%) in VL and 326 (91%) in CD4 were alive and on follow-up. The cumulative risk of clinical failure was 8.0% (95% CI 5.6–11.4) in VL versus 7.4% (5.1–10.7) in CD4, and the upper-limit of the one-sided 95% CI of the difference was 3.4%, meeting the pre-determined non-inferiority criterion. Probability of switch for study criteria was 5.2% (3.2–8.4) in VL versus 7.5% (5.0–11.1) in CD4 (p = 0.097). Median time from treatment initiation to switch was 11.7 months (7.7–19.4) in VL and 24.7 months (15.9–35.0) in CD4 (p = 0.001). The median duration of viremia >400 copies/ml at switch was 7.2 months (5.8–8.0) in VL versus 15.8 months (8.5–20.4) in CD4 (p = 0.002). FDO scores were not significantly different at time of switch. No adverse events related to the monitoring strategy were reported.
The 3-year rates of clinical failure and loss of treatment options did not differ between strategies although the longer-term consequences of CD4 monitoring would need to be investigated. These results provide reassurance to treatment programs currently based on CD4 monitoring as VL measurement becomes more affordable and feasible in resource-limited settings.
Trial registration
ClinicalTrials.gov NCT00162682
Please see later in the article for the Editors' Summary
Editors' Summary
About 34 million people (most of them living in low-and middle-income countries) are currently infected with HIV, the virus that causes AIDS. HIV infection leads to the destruction of immune system cells (including CD4 cells, a type of white blood cell), leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, most HIV-infected individuals died within 10 years of infection. Then, in 1996, highly active antiretroviral therapy (HAART)—combined drugs regimens that suppress viral replication and allow restoration of the immune system—became available. For people living in affluent countries, HIV/AIDS became a chronic condition but, because HAART was expensive, HIV/AIDS remained a fatal illness for people living in resource-limited countries. In 2003, the international community declared HIV/AIDS a global health emergency and, in 2006, it set the target of achieving universal global access to HAART by 2010. By the end of 2011, 8 million of the estimated 14.8 million people in need of HAART in low- and middle-income countries were receiving treatment.
Why Was This Study Done?
At the time this trial was conceived, national and international recommendations were that HIV-positive individuals should start HAART when their CD4 count fell below 200 cells/mm3 and should have their CD4 count regularly monitored to optimize HAART. In 2013, the World Health Organization (WHO) recommendations were updated to promote expanded eligibility for HAART with a CD4 of 500 cells/mm3 or less for adults, adolescents, and older children although priority is given to individuals with CD4 count of 350 cells/mm3 or less. Because HIV often becomes resistant to first-line antiretroviral drugs, WHO also recommends that viral load—the amount of virus in the blood—should be monitored so that suspected treatment failures can be confirmed and patients switched to second-line drugs in a timely manner. This monitoring and switching strategy is widely used in resource-rich settings, but is still very difficult to implement for low- and middle-income countries where resources for monitoring are limited and access to costly second-line drugs is restricted. In this randomized non-inferiority trial, the researchers compare the performance of a CD4-based treatment monitoring and switching strategy with the standard viral load-based strategy among HIV-positive adults in Thailand. In a randomized trial, individuals are assigned different interventions by the play of chance and followed up to compare the effects of these interventions; a non-inferiority trial investigates whether one treatment is not worse than another.
What Did the Researchers Do and Find?
The researchers assigned about 700 HIV-positive adults who were beginning HAART for the first time to have their CD4 count (CD4 arm) or their CD4 count and viral load (VL arm) determined every 3 months. Participants were switched to a second-line therapy if their CD4 count declined by more than 30% from their peak CD4 count (CD4 arm) or if a viral load of more than 400 copies/ml was recorded (VL arm). The 3-year cumulative risk of clinical failure (defined as death, a new AIDS-defining event, or a CD4 count of less than 50 cells/mm3) was 8% in the VL arm and 7.4% in the CD4 arm. This difference in clinical failure risk met the researchers' predefined criterion for non-inferiority. The probability of a treatment switch was similar in the two arms, but the average time from treatment initiation to treatment switch and the average duration of a high viral load after treatment switch were both longer in the CD4 arm than in the VL arm. Finally, the future-drug-option score, a measure of viral drug resistance profiles, was similar in the two arms at the time of treatment switch.
What Do These Findings Mean?
These findings suggest that, in Thailand, a CD4 switching strategy is non-inferior in terms of clinical outcomes among HIV-positive adults 3 years after beginning HAART when compared to the recommended viral load-based switching strategy and that there is no difference between the strategies in terms of viral suppression and immune restoration after 3-years follow-up. Importantly, however, even though patients in the CD4 arm spent longer with a high viral load than patients in the VL arm, the emergence of HIV mutants resistant to antiretroviral drugs was similar in the two arms. Although these findings provide no information about the long-term outcomes of the two monitoring strategies and may not be generalizable to routine care settings, they nevertheless provide reassurance that using CD4 counts alone to monitor HAART in HIV treatment programs in resource-limited settings is an appropriate strategy to use as viral load measurement becomes more affordable and feasible in these settings.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001494.
The World Health Organization provides information on all aspects of HIV/AIDS (in several languages); its 2010 recommendations for antiretroviral therapy for HIV infection in adults and adolescents are available as well as the June 2013 Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach
The 2012 UNAIDS World AIDS Day Report provides up-to-date information about the AIDS epidemic and efforts to halt it
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS and summaries of recent research findings on HIV care and treatment
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on the global HIV/AIDS epidemic, on HIV and AIDS in Thailand, on universal access to AIDS treatment, and on starting, monitoring and switching HIV treatment (in English and Spanish)
The UK National Health Service Choices website provides information (including personal stories) about HIV and AIDS
More information about this trial (the PHPT-3 trial) is available
Patient stories about living with HIV/AIDS are available through Avert; the nonprofit website Healthtalkonline also provides personal stories about living with HIV, including stories about HIV treatment
Related Articles
Adherence and plasma HIV RNA responses to highly active antiretroviral therapy among HIV-1 infected injection drug users
Wood, Evan
Montaner, Julio S.G.
Yip, Benita
Tyndall, Mark W.
Schechter, Martin T.
O'Shaughnessy, Michael V.
Hogg, Robert S.
CMAJ: Canadian Medical Association Journal
The benefits of highly active antiretroviral therapy (HAART) for the treatment of HIV infection are well documented, but concerns regarding access and adherence to HAART are growing. We evaluated virological responses to HAART among HIV-1 infected patients who were injection drug users (IDUs) in a population-based setting where HIV/AIDS care is delivered free of charge.
We evaluated previously untreated HIV-1 infected men and women who initiated HAART between Aug. 1, 1996, and July 31, 2000, and who were followed until Mar. 31, 2002, in a province-wide HIV treatment program. We used Kaplan–Meier methods and Cox proportional hazards regression in our evaluation of time to suppression (i.e., less than 500 copies/mL) and rebound (i.e., 500 copies/mL or more) of plasma HIV-1 RNA, with patients stratified according to whether or not they had a history of injection drug use.
Overall, 1422 patients initiated HAART during the study period, of whom 359 (25.2%) were IDUs. In Kaplan–Meier analyses, the cumulative suppression rate at 12 months after initiation of HAART was 70.8% for non-IDUs and 51.4% for IDUs (p < 0.001) (these values include people who achieved suppression before 12 months but who might not have been followed for the full 12-month period). Among patients who achieved suppression of plasma HIV-1 RNA, the cumulative rebound rate at 12 months after initial suppression was 23.8% for non-IDUs and 34.7% for IDUs (p < 0.001). However, after adjustment for adherence and other covariates, the rates of HIV-1 RNA suppression (adjusted relative hazard 0.9, 95% confidence interval [CI] 0.7–1.0) and HIV-1 RNA rebound (adjusted relative hazard 1.3, 95% CI 1.0–1.6) were similar between non-IDUs and IDUs. Differences between non-IDUs and IDUs were even less pronounced in subanalyses that considered only therapy-adherent patients (p > 0.1).
Non-IDUs and IDUs had similar rates of HIV-1 RNA suppression and rebound after the initiation of HAART, once lower levels of adherence were taken into account. Nevertheless, the lower virological response rates among IDUs suggest that, unless interventions are undertaken to improve adherence, these patients may experience elevated rates of disease progression and use of medical services in our setting.
Related Articles
The Impact of Kidney Function at HAART Initiation on Mortality in HIV-infected Women
Estrella, Michelle M.
Parekh, Rulan S.
Abraham, Alison
Astor, Brad C.
Szczech, Lynda A.
Anastos, Kathryn
Dehovitz, Jack A.
Merenstein, Daniel J.
Pearce, C. Leigh
Tien, Phyllis C.
Cohen, Mardge H.
Gange, Stephen J.
Journal of acquired immune deficiency syndromes (1999)
In the early highly active antiretroviral therapy (HAART) era, kidney dysfunction was strongly associated with death among HIV-infected individuals. We re-examined this association in the later HAART period to determine whether chronic kidney disease (CKD) remains a predictor of death after HAART-initiation.
To evaluate the effect of kidney function at the time of HAART initiation on time to all-cause mortality, we evaluated 1415 HIV-infected women initiating HAART in the Women's Interagency HIV Study (WIHS). Multivariable proportional hazards models with survival times calculated from HAART initiation to death were constructed; participants were censored at the time of the last available visit or December 31, 2006.
CKD (eGFR <60 ml/min/1.73 m2) at HAART initiation was associated with higher mortality risk adjusting for age, race, hepatitis C serostatus, AIDS history and CD4+ cell count (hazard ratio [HR]=2.23, 95% confidence interval [CI]: 1.45–3.43). Adjustment for hypertension and diabetes history attenuated this association (HR=1.89, CI: 0.94–3.80). Lower kidney function at HAART initiation was weakly associated with increased mortality risk in women with prior AIDS (HR=1.09, CI: 1.00–1.19, per 20% decrease in eGFR).
Kidney function at HAART initiation remains an independent predictor of death in HIV-infected individuals, especially in those with a history of AIDS. Our study emphasizes the necessity of monitoring kidney function in this population. Additional studies are needed to determine mechanisms underlying the increased mortality risk associated with CKD in HIV-infected persons.
kidney disease; mortality; HIV; WIHS; antiretroviral therapy
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text:
According to new waves and ideas in programming, parser-blade conception becomes archaic.
I will start new project of next generation CMS soon.
According to GPL, all sources is still free.
Project closed. Thanks to all for assistance.
SQL server cannot be connected.
Try parser-blade-0.4.1
gbook is a simple guestbook for parser-blade. Enjoy.
First alpha in russian only.
It's simple, but effective. Modules are discriminated by the path, and site adnib can install several same modules. Main page will be a module too. First version of BP will not contains blocks (like PHPNuke), they will be added later.
The release will be done at the end of february.
I had some problems with my internet connetcion, but the project is still alive, and today I updated CVS with a new version. The first version of PB API will be ready soon.
I have made first release - version 0.1.
Now I going to make some... preparations. I will correct the roadmap and API. API docs will be placed here, when it`s done.

subset: commoncrawl


text: There is no header <th> showing up for the follow/mute button next to each forum topic. I see the code for it in the PHP file. The follow/mute link text appears on the far right of each topic but the header is blank. When looking for the style in Firebug it does not exist. Has anyone else had a problem with this? Any help would be greatly appreciated. Thanks.


text:
Quick shots – Crysis 3 lighting artist shares new shots
Below thr break you'll find four extremely shiny new screenshots from Crysis 3.
The images are signed by Pierre-Yves Donzallaz but do not appear on the Crytek lighting artist's portfolio; TinEye didn't return a result either. Very mysterious. We found them on Evil Avatar.
Crysis 3 hits PC, PlayStation 3 and Xbox 360 in February 2013.
Sometimes we include links to online retail stores. If you click on one and make a purchase we may receive a small commission. For more information, go here.


text:
Vanderbilt Commodores (8-4) vs. Houston Cougars (8-4)
Jan. 4, 1 p.m. ET, Birmingham, Ala. (ESPN)
Coach James Franklin has turned his revival of the Vanderbilt program into a new golden age. These are heady times for the Commodores. Vandy recently completed yet another unbeaten November, giving it a nine-game winning streak in that critical month that dates to 2011.
Vanderbilt defeated Georgia and Florida for the first time in the same season, picking up the school's first road win against the Gators since 1945. VU's only SEC East losses were to the top two teams -- South Carolina and Missouri.
Despite a nail-biting loss in the season opener against Ole Miss and a big road loss to Texas A&M, the Dores won eight games and went .500 in the SEC. VU has eight wins in back-to-back regular seasons for the first time since 1927-28 and is making its third straight bowl appearance. Here's some perspective: Before Franklin arrived, Vanderbilt had been to four bowl games in 120 years.
The Commodores have a balanced offense that features the passing combination of quarterback Austyn Carta-Samuels to wide receiver Jordan Matthews. But this year has seen more emphasis on running the ball, as Vandy employs a committee that includes leading rusher Jerron Seymour, Brian Kimbrow, Wesley Tate and lately more designed runs for Carta-Samuels and backup QB Patton Robinette. The biggest star and most dangerous player, however, is the silky-smooth Matthews, who has an SEC-record 18 career 100-yard games and broke his own school record this season with 1,334 yards receiving (fifth most in SEC history).
Perhaps the biggest strides the program has made this season have been on the other side of the ball, where Vanderbilt has allowed 333.9 yards a game to rank No. 19 in the nation in total defense. This is an opportunistic bunch with 26 takeaways. On the whole, Franklin runs a tight ship. His offense doesn't give up the ball very often (20 turnovers on the year) and averages just more than five penalties a game.
In other words, Vanderbilt rarely beats itself. -- Jeff Barlis
The Cougars have quietly had a nice turnaround season, sitting at 8-4 in coach Tony Levine's second season after a 5-7 campaign in 2012.
Houston has improved in a number of areas, especially on defense. It leads the country in turnover margin (+25) and takeaways (40) under defensive coordinator David Gibbs.
Each of the Cougars' four losses have come by seven points or fewer -- not bad for a team with a true freshman quarterback (John O'Korn).
While he's had some growing pains, O'Korn has been solid (26 touchdowns, eight interceptions) and he has many weapons at his disposal, namely sophomore receiver Deontay Greenberry (76 receptions, 1,106 yards, 10 touchdowns).
One note: Offensive coordinator Doug Meacham has accepted the same job at TCU so co-OC Travis Bush will call the plays in the bowl game. -- Sam Khan Jr.


text:
OKLAHOMA CITY (AP) - The Oklahoma Attorney General's office is
looking into concerns that Canadian oil is being dumped on Oklahoma
markets, driving down the price Oklahoma oil producers receive for their product.
Attorney General Drew Edmondson says he has opened a preliminary
inquiry into whether this is a violation of state and federal antitrust laws.
A spokesman for the Oklahoma Independent Petroleum Association says a Canadian pipeline runs directly into Cushing, where as much as 10 percent of the nation's oil is stored.
With storage in Cushing reaching capacity, OIPA spokesman Cody
Bannister says the price paid to Oklahoma producers is being driven
down below market levels.


text:
Ray Florence, 77, of Saint John's, passed away June 13, 2007. A native of Salt Lake City, Utah, Ray had lived in Saint Johns for the past five years.
He is survived by his loving wife, Jody Florence; daughter, Terri Gurzi; and grandchildren, Megan Gurzi and Cassi (Eric) Tansey, all of Saint Johns. Also surviving are six children, 11 grandchildren, two great-grandchildren and one sister living in other parts of the country. A memorial service will be held at a later date in Salt Lake City, Utah.
Hardage-Giddens Mandarin Funeral Home in Jacksonville is serving the family.
© 2016. All Rights Reserved. Contact Us


text:
Studio event this weekend!
We are looking forward to a busy weekend at the Morpheus Glass Open Studio event. We have loads of work on show, including lots of new designs and colours and have some fantastic offers on for the weekend! We hope you can make it along for a visit.


text:
They go out and address quality−of−life crimes and wind up making a difference.
Dep. Inspector Ralph Monteforte honored the 70th Precinct's two conditions teams as "Cops of the Month" at the recent community council meeting.
Since their formation about six months ago, the two teams consisting of two sergeants and 15 police officers have made over 600 misdemeanor or felony arrests and have taken four guns off the street, said Monteforte.
Monteforte explained that besides addressing quality−of−life concerns such as noise complaints, marijuana and drinking in public, the conditions team also goes to areas of concern in the precinct where there might be clusters of crime.
Monteforte said the conditions unit is picked from the best patrol officers and then the team works seven days a week at various hours.
They address conditions brought to the precinct's attention from either 311 complaints or from patrol officers.
"So every day they are doing something different," said Monteforte, adding they are a major reason crime is down over 22 percent for the year in the precinct.
Monteforte said that once the precinct is alerted to a crime condition, he decides whether the conditions team, anti−crime unit, community policing unit (CPU) or youth officers should be deployed to the area.
If the incident involves a shooting, all units in the command will try to lock up those people, he said.
Monteforte said these various units take down reports and the unsolved crimes goes to the detective bureau, which does investigations.
With the summer around the corner, Monteforte said he expects to deploy the conditions team at times around the Prospect Park Parade Grounds where summer athletic leagues are in full swing.
©2009 Community News Group
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Cate Blanchett has adorned many a hat in her acting career, from an elf queen to an aging woman, to a ruthless government operative. It shall only be fair to say that, she is one of the most talented actresses showbiz has seen in a long long time. Therefore it can only be considered great news, when someone like her is brought in as a guest star or rather guest voice in a popular show like Family Guy. It isn't really a secret that stars one in a while like to get in touch with their zany side, and want to prove to the audiences that they too have a funny bone in them.
What better way for them to do the proving, than voice characters on popular animated shows like the Simpsons or Family Guy. In fact it wouldn't be wrong to say that, this trend was started by the Simpsons, with nearly every big movie and TV star having made a guest appearance on the show, at one point of time or the other. So come this Sunday and Cate Blanchett's voice would greet you in your living room that is if you put on Family Guy. The character you need to look out for on the show is a girl called Penelope, who would be featured as Stewie's newest bud. Surely, the Oscar winner will voice Penelope in her own inimitable style, becoming Penelope's voice rather than Penelope sounding like Cate Blanchett.
In the show Penelope would not only be bonding with Stewie but would also be having a boat load of fun. A case in point is a part where Stewie and Penelope plant an exploding wallet on Mort, who is none the wiser. They then stalk him, with the both of them maniacally giggling, at the thought of having played such a joke.
Source: Vulture


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Millefiore...A thousand flowers
This versatile beaded trio is marvelously decorative, like the millefiore, or thousand-flowered beads that originated in Italy. Millefiore beads look very mandala-like, and I thought it a very appropriate name for a beautifully beaded garment that is knit entirely in the round. Pattern is written and charted. Beads are added by two methods: pre-stringing and the crochet hook add-as-you-go technique.
In each piece, the lace pattern begins at the bottom with a scallop, then becomes a charming textured lace pattern that is lightly shaped as it goes up toward the top. Wimple is long enough to gently cover the head. Wristlets can be worn either way: scallops extending over the hand, or toward the elbow.
View more Accessories, Beaded, Ensembles, Neckwear patterns
View all patterns


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"Welcome to Medyka" Medyka by yumyum
Medyka Travel Guide: 6 reviews and 14 photos
We didn't plan to visit Medyka but since we crossed the Polish/Ukrainian border here on our way to Lviv in Ukraine we knew that there is a wooden church which we saw from the bus. Since by chance we came back from Lviv the same way we walked to the towncenter from the nearby border post and visited before heading onwards.
Medyka goes back to the 14th century and was often visited by the Polish king Ladilaus Jagiello.
- In a nutshell:Take a break if you are in the area!
Reviews (6)
After passing "downtown" Medyka and just before you go underneath the railway line you will find the Grunwald monument.... more travel advice
In Przemysl you will find the mini-buses to the border in Medyka when you come up from the underground passage from the... more travel advice
Near the wooden church on the main road we also noticed the old synagogue which is only a ruin. But you can still... more travel advice
Right next to the wooden church you will find the new modern church which is much bigger. Still, it's not big enough for... more travel advice
Comments (11)
Looks like an interesting little place!
looks like an interesting little stopover.
Truly a destination off the beaten path! Thanks for a lovely page!
What a pretty wooden church! Right up my alley :-)
Hello, Sonja! It was great you had that chance! Thanks for your story and photographs! ><><><
How interesting to read about what you were doing while we were on the train that day! The church looks interesting - a good detour. We saw some storks' nests from the train but it was harder to photoraph them when moving of course
interesting architecture
Very interesting little page, Sonja! Congratulations with the victory of the Swiss national football team over Spain in the South Africa!
Ladislaus Jagiello? Wasn't he also the grand duke of Lithuania? (I didn't really know that, just googled him.) While you were in Poland I went to Z�rich again, will add some more tips when I have time.
an interesting off-the-beaten path-place, thanks for sharing, Sonja !
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Franck Boclet Men's RTW Fall 2011
Asymmetrical wool military coats; biker jackets; and kimono-inspired dinner jackets figured among Franck Boclet's outerwear-focused Milan debut.
— January 18, 2011
Franck Boclet Men's RTW Spring 2011
The debut signature collection from Boclet offered an array of relaxed tailored looks for spring.
— June 24, 2010
- Page
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text:
Tech Netscape is Dead
posted by December 28 at 16:12 PMon
Netscape is no more.
Netscape, the Web browser once used in 80 percent of all Internet sessions, will be shut down by AOL after failing to regain market share from Microsoft Corp.'s Internet Explorer.
Netscape users should switch to Mozilla Foundation's Firefox browser, Netscape director Tom Drapeau wrote on his blog. America Online Inc. paid $9.8 billion in 1999 for Netscape, which by then had been crippled by Microsoft.
You gotta love this quote…
"AOL's focus on transitioning to an ad-supported Web business leaves little room for the size of investment needed to get the Netscape browser to a point many of its fans expect it to be," Drapeau said.
Netscape had fans? And who's gonna shut down AOL after its transition to an "ad-supported Web business" ultimately fails?