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.
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.
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
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.
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.
We evaluated pain frequency and severity in 339 women enrolled in the Women’s Interagency HIV Study (WIHS). Among these, 63% were 39 years of age or younger, 17% were white, 54% African American, and 29% Hispanic; 32% did not complete high school; 58% had a CD4 less than 200; 65% had clinical AIDS; 60% were on highly active antiretroviral therapy (HAART); and 32% had a viral load of 50,000 or more. Data were collected between 1996 and 1998. Within the past 6 months 190 (56%) women experienced pain 6 or more days and 168 (50%) women indicated pain severity scores of 4 or 5 (5-point scale). Pain frequency and pain severity were not associated with age, education, ethnicity, current therapy, or location of the WIHS site. Pain frequency and severity were related to lower CD4 count, higher depression, with a history and longer duration of smoking and use of marijuana. Severity was associated with a history of crack/cocaine or heroin use or with injection drug use as the transmission category. In the multivariate models, pain severity was related to CD4 count and depression and to current tobacco use but not to crack, cocaine, heroin, or marijuana use. Pain frequency was related to depression and to former tobacco, crack, cocaine, heroin, or marijuana use but not to current use. The long-term effects of tobacco use may be to increase pain experience but women may also smoke tobacco or use other substances to give mild pain relief. Pain is frequent and often severe among women with HIV requiring medical management.
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
We evaluated pain frequency and severity in 339 women enrolled in the Women's Interagency HIV Study (WIHS). Among these, 63% were 39 years of age or younger, 17% were white, 54% African American, and 29% Hispanic; 32% did not complete high school; 58% had a CD4 less than 200; 65% had clinical AIDS; 60% were on highly active antiretroviral therapy (HAART); and 32% had a viral load of 50,000 or more. Data were collected between 1996 and 1998. Within the past 6 months 190 (56%) women experienced pain 6 or more days and 168 (50%) women indicated pain severity scores of 4 or 5 (5-point scale). Pain frequency and pain severity were not associated with age, education, ethnicity, current therapy, or location of the WIHS site. Pain frequency and severity were related to lower CD4 count, higher depression, with a history and longer duration of smoking and use of marijuana. Severity was associated with a history of crack/cocaine or heroin use or with injection drug use as the transmission category. In the multivariate models, pain severity was related to CD4 count and depression and to current tobacco use but not to crack, cocaine, heroin, or marijuana use. Pain frequency was related to depression and to former tobacco, crack, cocaine, heroin, or marijuana use but not to current use. The long-term effects of tobacco use may be to increase pain experience but women may also smoke tobacco or use other substances to give mild pain relief. Pain is frequent and often severe among women with HIV requiring medical management.
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.
Background and purpose
Human immunodeficiency virus (HIV)-infected persons taking highly active antiretroviral therapy (HAART) may have an increased risk for cardiovascular-related events, although the underlying mechanism remains unclear. We tested the hypothesis that carotid arterial stiffness was higher among persons taking HAART compared to HAART-naïve and HIV-uninfected persons.
Between 2004 and 2006, we performed high resolution B-mode ultrasound on 2,789 HIV-infected and HIV-uninfected participants of the Women’s Interagency HIV Study (WIHS; 1865 women) and the Multicenter AIDS Cohort Study (MACS; 924 men) and determined carotid arterial distensibility, a direct measure of carotid arterial stiffness. We used generalized estimating equations to evaluate the association between distensibility and HIV infection, CD4+ cell count, and exposure to HAART adjusted for demographic, behavioral, and clinical characteristics.
In multivariable analysis, distensibility was 4.3% lower (95% confidence interval (CI): -7.4% to -1.1%) among HIV-infected versus uninfected participants. Among HIV-infected participants with fewer than 200 CD4+ cells, distensibility was 10.5% lower (95% CI: -14.5% to -6.2%) than that among HIV-uninfected participants, and this effect did not differ significantly by cohort or race. Concurrent HAART use was independently associated with lower distensibility among MACS participants but not among WIHS participants.
Our finding that advanced HIV-related immunosuppression was associated with increased carotid arterial stiffness independent from the effects of traditional atherosclerosis risk factors suggests that the etiologic mechanism underlying reports of an increased cardiovascular disease risk among HIV-infected individuals might involve HIV-related immunosuppression leading to vascular dysfunction and arterial stiffening.
atherosclerosis; cardiovascular disease; carotid arteries; HIV; epidemiology
To evaluate the effects of longitudinal patterns and types of non-injection drug use (NIDU) on HIV progression in the highly active antiretroviral therapy (HAART) era.
Women’s Interagency HIV Study (WIHS), a prospective cohort study conducted at six US sites.
Data were collected semi-annually from 1994 to 2002 on 1046 HIV+ women. Multivariate Cox proportional hazards modeling was used to estimate relative hazards for developing AIDS and for death by pattern and type of NIDU.
During follow-up, 285 AIDS events and 287 deaths, of which 177 were AIDS-related, were reported. At baseline, consistent and former NIDU was associated with CD4+ counts of < 200 cells/μl (43% and 46%, respectively) and viral load > 40 000 copies/ml (53% and 55%, respectively). Consistent NIDU reported less HAART use (53%) compared with other NIDU patterns. Stimulant use was associated with CD4+ cell counts of < 200 cells/μl (53%) and lower HAART initiation (63%) compared with other NIDU types. In multivariate analyses, progression to AIDS was significantly higher among consistent (RH = 2.52), inconsistent (RH = 1.63) and former (RH = 1.56) users compared with never users; and for stimulant (RH = 2.04) and polydrug (RH = 1.65) users compared with non-users. Progression to all-cause death was higher only among former users (RH = 1.48) compared with never users in multivariate analysis. NIDU behaviors were not associated with progression to AIDS-related death.
In this study, pattern and type of NIDU were associated with HIV progression to AIDS and all-cause mortality. These differences were associated with lower HAART utilization among consistent NIDU and use of stimulants, and poor baseline immunological and virological status among former users.
Acquired immunodeficiency syndrome; highly active anti-retroviral therapy; human immunodeficiency virus; mortality; non-injection drug use
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).
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.
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
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
Inflammation and hemostasis perturbation may be involved in vascular complications of HIV infection. We examined atherogenic biomarkers and subclinical atherosclerosis in HIV-infected adults before and after beginning highly-active antiretroviral therapy (HAART).
In the Women's Interagency HIV Study (WIHS), 127 HIV-infected women studied pre- and post-HAART were matched to HIV-uninfected controls. Six semi-annual measurements of soluble CD14, tumor necrosis factor (TNF)-alpha, soluble interleukin (IL)-2 receptor, IL-6, IL-10, monocyte chemoattractant protein (MCP)-1, D-dimer, and fibrinogen were obtained. Carotid artery intima-media thickness (CIMT) was measured by B-mode ultrasound.
Relative to HIV-uninfected controls, HAART-naïve HIV-infected women had elevated levels of soluble CD14 (1945 vs 1662 ng/mL, Wilcoxon signed rank P<0.0001), TNF-alpha (6.3 vs 3.4 pg/mL, P<0.0001), soluble IL-2 receptor (1587 vs 949 pg/mL, P<0.0001), IL-10 (3.3 vs 1.9 pg/mL, P<0.0001), MCP-1 (190 vs 163 pg/mL, P<0.0001) and D-dimer (0.43 vs 0.31 µg/mL, P<0.01). Elevated biomarker levels declined after HAART. While most biomarkers normalized to HIV-uninfected levels, in women on effective HAART, TNF-alpha levels remained elevated compared to HIV-uninfected women (+0.8 pg/mL, P=0.0002). Higher post-HAART levels of soluble IL-2 receptor (P=0.02), IL-6 (P=0.05), and D-dimer (P=0.03) were associated with increased CIMT.
Untreated HIV infection is associated with abnormal hemostasis (e.g., D-dimer), and pro-atherogenic (e.g., TNF-alpha) and anti-atherogenic (e.g., IL-10) inflammatory markers. HAART reduces most inflammatory mediators to HIV-uninfected levels. Increased inflammation and hemostasis are associated with subclinical atherosclerosis in recently treated women. These findings have potential implications for long-term risk of cardiovascular disease in HIV-infected patients, even with effective therapy.
antiretroviral therapy; cardiovascular diseases; cytokines; hemostasis; HIV; inflammation
Highly active antiretroviral therapy (HAART) rapidly suppresses human immunodeficiency virus (HIV) viral replication and reduces circulating viral load, but the long-term effects of HAART on viral load remain unclear.
We evaluated HIV viral load trajectories over 8 years following HAART initiation in the Multicenter AIDS Cohort Study and the Women’s Interagency HIV Study. The study included 157 HIV-infected men and 199 HIV-infected women who were antiretroviral naïve and contributed 1311 and 1837 semiannual person-visits post-HAART, respectively. To account for within-subject correlation and the high proportion of left-censored viral loads, we used a segmental Bernoulli/lognormal random effects model.
Approximately 3 months (0.30 years for men and 0.22 years for women) after HAART initiation, HIV viral loads were optimally suppressed (ie, with very low HIV RNA) for 44% (95% confidence interval = 39%–49%) of men and 43% (38%–47%) of women, whereas the other 56% of men and 57% of women had on average 2.1 (1.5–2.6) and 3.0 (2.7–3.2) log10 copies/mL, respectively.
After 8 years on HAART, 75% of men and 80% of women had optimal suppression, whereas the rest of the men and women had suboptimal suppression with a median HIV RNA of 3.1 and 3.7 log10 copies/mL, respectively.
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.
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.
Mu opioid receptor (OPRM1) ligands may alter expression of chemokines and chemokine receptors involved in penetration of human immunodeficiency virus (HIV) type 1 into the cell. We suggest that OPRM1 variants may affect the pathophysiology of HIV infection.
DNA samples from 1031 eligible African Americans, Hispanics, and whites from the Women's Interagency HIV Study (WIHS) who were alive as of April 2006 were analyzed. We performed regression analysis of association of 18 OPRM1 variants with a change of viral load and CD4 cell count during 2 periods: between admission to WIHS and the start of highly active antiretroviral therapy (HAART) (interval X) and between the start of HAART and the most recent WIHS visit (interval Y), and examined the association of these variants with HIV status.
Regardless of genotype, a significant decrease in viral load during interval X was found for each ethnicity. Whites with allele G of the functional polymorphism 118A > G (reference sequence rs1799971) showed a smaller decrease in viral load; those bearing minor alleles IVS1 + 1050A, IVS1 + 14123A, and IVS2 + 31A showed a larger decrease in viral load over interval X (0.01 < P < .05). Hispanics with the same alleles showed a greater increase in CD4 cell count over interval Y (0.01 < P < .05). We found an association between OPRM1 variants and HIV status in African Americans and whites.
OPRM1 polymorphisms may alter the severity of HIV infection before and after HAART.
Relationships between non-use of highly active anti-retroviral therapy (HAART), race/ethnicity, violence, drug use and other risk factors are investigated using qualitative profiles of five risk factors (unprotected sex, multiple male partners, heavy drinking, crack, cocaine or heroin use, and exposure to physical violence) and association of the profiles and race/ethnicity with non-use of HAART over time.
A Hidden Markov Model (HMM) was used to summarize risk factor profiles and changes in profiles over time in a longitudinal sample of HIV-infected women enrolled in the Women's Interagency HIV Study (WIHS) with follow-up from 2002 to 2005 (N=802).
Four risk factor profiles corresponding to four distinct latent states were identified from the five risk factors. Trajectory analysis indicated that states characterized by high probabilities of all risk factors or by low probabilities of all risk factors were both relatively stable over time. Being in the highest risk state did not significantly elevate the odds of HAART non-use (OR: 1.05; 95% CI: 0.6-1.8). However, being in a latent state characterized by elevated probabilities of heavy drinking and exposure to physical violence, along with slight elevations in three other risk factors, significantly increased odds of HAART non-use (OR: 1.4; 95% CI: 1.1-1.9).
The research suggests that HAART use might be improved by interventions aimed at women who are heavy drinkers with recent exposure to physical violence and evidence of other risk factors. More research about the relationship between clustering and patterns of risk factors and use of HAART is needed.
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
In HIV-infected pregnant women, viral suppression prevents mother-to-child HIV transmission. Directly observed highly-active antiretroviral therapy (HAART) enhances virological suppression, and could prevent transmission. Our objective was to project the effectiveness and cost-effectiveness of directly observed administration of antiretroviral drugs in pregnancy.
Methods and Findings
A mathematical model was created to simulate cohorts of one million asymptomatic HIV-infected pregnant women on HAART, with women randomly assigned self-administered or directly observed antiretroviral therapy (DOT), or no HAART, in a series of Monte Carlo simulations. Our primary outcome was the quality-adjusted life expectancy in years (QALY) of infants born to HIV-infected women, with the rates of Caesarean section and HIV-transmission after DOT use as intermediate outcomes. Both self-administered HAART and DOT were associated with decreased costs and increased life-expectancy relative to no HAART. The use of DOT was associated with a relative risk of HIV transmission of 0.39 relative to conventional HAART; was highly cost-effective in the cohort as a whole (cost-utility ratio $14,233 per QALY); and was cost-saving in women whose viral loads on self-administered HAART would have exceeded 1000 copies/ml. Results were stable in wide-ranging sensitivity analyses, with directly observed therapy cost-saving or highly cost-effective in almost all cases.
Based on the best available data, programs that optimize adherence to HAART through direct observation in pregnancy have the potential to diminish mother-to-child HIV transmission in a highly cost-effective manner. Targeted use of DOT in pregnant women with high viral loads, who could otherwise receive self-administered HAART would be a cost-saving intervention. These projections should be tested with randomized clinical trials.
To evaluate the impact of hepatitis C virus (HCV) on the immune system before receipt of highly active antiretroviral therapy (HAART) and on immune recovery after receipt of HAART among human immunodeficiency virus (HIV)/HCV–coinfected women enrolled in the Women’s Interagency HIV Study.
The study included 294 HIV-infected women who initiated HAART and attended 2 follow-up visits. The women were grouped on the basis of positive HCV antibody and HCV RNA tests. There were 148 women who were HCV antibody negative, 34 who were HCV antibody positive but RNA negative, and 112 who were HCV antibody and RNA positive. Immune recovery was measured by flow-cytometric assessment for markers of activation and maturation on CD4+ and CD8+ T cells. Data analysis used repeated measures of variance.
HIV/HCV coinfection is associated with an increased number of CD4+ and CD8+ primed/memory T cells. HIV/HCV coinfection, however, did not affect any further decreases in CD4+ or CD4+ and CD8+ naive/memory T cell counts or enhanced T cell activation. HIV/HCV coinfection also did not affect HAART responses in the CD4+ and CD8+ T cell compartment.
HCV does not affect immune responses to HAART in HIV/HCV–coinfected individuals but is associated with an expansion of CD4+ and CD8+ memory T cell subsets. Functional impairment in the CD4+ and CD8+ T cell compartments still needs to be assessed in coinfected patients.
Human immunodeficiency virus (HIV)–infected individuals frequently have consumed garlic, a popular complementary supplement. Researchers rarely have studied garlic’s association with antiretroviral therapies, however, even though that association is very relevant clinically.
To examine associations of supplemental use of garlic with highly active antiretroviral treatment (HAART) adherence level and HAART effectiveness (HIV viral load and CD4+ cell counts) in HIV-infected women.
The research team carried out a self-controlled, longitudinal study nested within the Women’s Interagency HIV Study (WIHS). The team used a paired study design that allowed participants to serve as their own controls. The team first identified all of the study’s visits in which the participant self-reported the use of a garlic supplement since her last visit (index visit). Then for each index visit, the team identified a matching visit (a control visit) using the following criteria: (a) the visit must be one for the same participant in which that participant reported no garlic supplementation; (b) the visit must immediately precede the index visit (less than 1 year apart); and (c) at the time of the control visit, the participant must have been using antiretroviral therapy identical to that used at the time of the index visit.
Participants were persons using garlic supplementation who already were participants in the WIHS.
The research team used a logistic regression model to examine the association between garlic supplementation and HAART adherence level. The team used a mixed linear model to examine the association of garlic supplementation with HIV viral load and CD4+ cell counts.
From October 1994 to April 2009, 390 HIV-infected women in the WIHS made 1112 visits at which they reported using garlic supplements. Seventy-seven HIV-infected women using HAART met the research team’s selection criteria and contributed 99 pairs of visits for the study. Among the women who used garlic supplements, 22% were 50 years and older; 58% were black and non-Hispanic; and 23% had less than a high-school education. Neither use of garlic supplementation nor reasons for using garlic supplements were significantly associated with the HAART adherence level, HIV viral load, or CD4+ cell counts; however, “use garlic as needed,” a potential marker of a disease state, was significantly associated with higher viral load (P = .0003).
Short-term garlic supplementation did not impact HAART adherence level, HIV viral load, and CD4+ cell counts.
Aims and Objectives:
To assess the prevalence of metabolic syndrome (MetS) in human immunodeficiency virus (HIV) positive patients. Prevalence of MetS was compared in patients who were not on highly active antiretroviral therapy (HAART) to patients who were on HAART.
Materials and Methods:
Seventy HIV positive cases were studied. Pregnant and lactating women, patients on drugs other than HAART known to cause metabolic abnormalities and those having diabetes or hypertension were excluded. Cases were evaluated for MetS by using National Cholesterol Education Program Adult Treatment Panel-III.
47 cases were on HAART and 23 cases were not on HAART. Fasting Blood Glucose ≥100 mg/dl was present in 28.6% cases, out of whom 27.7% were on HAART and 30.4% were not on HAART (P = 0.8089). 12.9% cases had BP ≥130/≥85 mm Hg, out of whom 14.9% were on HAART and 8.7% were not on HAART (P = 0.4666). 42.9% cases had TG ≥150 mg/dl, out of whom 44.7% were on HAART and 39.1% were not on HAART (P = 0.6894). HDL cholesterol was low (males <40 mg/dl, females <50 mg/dl) in 50% cases, out of whom 55.3% were on HAART and 39.1% were not on HAART (P = 0.2035).
Prevalence of MetS was 20%. Majority of patients had only one component of MetS (32.9%). Low HDL was present in 50%, followed by raised triglycerides in 42.9%. Waist circumference was not increased in any of the patients. There was no statistically significant difference between those on HAART and those not on HAART in distribution of risk factors and individual components of MetS.
Highly active antiretroviral therapy; human immunodeficiency virus; metabolic syndrome