A Paradigm Shift to Prevent HIV Drug Resistance

David Bangsberg discusses a new observational cohort study in nine countries in southern Africa that compares CD4 counts versus adherence to antiretroviral drugs for predicting virologic failure

Alcohol use and HIV serostatus of partner predict high-risk sexual behavior among patients receiving antiretroviral therapy in South Western Uganda

Background: Antiretroviral treatment restores the physical and immunological function for patients with HIV/AIDS and the return of sexual desire. The frequency and correlates of sexual activity among patients receiving ART have not been widely studied. There is concern that widespread availability of ART may result in sexual disinhibition including practice of high-risk sexual behavior. We determined the correlates of sexual activity and high-risk sexual behavior in an ART-treated population in rural and urban Uganda. Methods: We conducted a cross-sectional study among 329 ART-treated adult patients at two hospitals, one located in rural and another in urban western Uganda. We collected data on sexual activity, frequency of condom use, pregnancy, viral load (VL) and CD4. Patients were considered sexually active if they had had sexual intercourse in the last 6 months. Any unprotected sex was considered high-risk sex. A two-stage logistic regression was performed to determine factors associated with sexual activity and high-risk sex among those sexually active. Results: Overall, 222 (67%) patients were women, 138 (41.2%) had been on ART for at least one year, and 168 (51.4%) were sexually active of whom 127 (75.6%) used condoms at the last intercourse. Younger age (<=30 years) (Odds ratio; OR=2.3, 95% CI 1.2, 4.2), higher monthly income (OR=4.1, 95% CI 2.4, 7.4), and being married (OR=22.7, 95% CI 8.2, 62.9) were associated with being sexually active. Undetectable VL, CD4 count and treatment duration were not significantly associated with sexual activity. Among the sexually active, alcohol consumption (OR=3.3, 95% CI 1.2, 9.1) and unknown serostatus of partner (OR=5.8, 95% CI 1.5, 21.4) were significant predictors of high-risk sexual behavior. The frequency of unprotected sex at the last intercourse was 25.9% and 22.1% among the men and women respectively and was not significantly different (p value for chi square test =0.59). Conclusion: Younger persons receiving ART are more likely to be sexually active. ART clients are more likely to engage in unprotected sex when sero-status of partner is unknown or report use of alcohol. Counseling on alcohol use and disclosure of sero-status may be useful in reducing high risk sexual behavior

Harnessing Poverty Alleviation to Reduce the Stigma of HIV in Sub-Saharan Africa

Alexander Tsai and colleagues highlight the complex relationship between poverty and HIV stigma in sub-Saharan Africa, and discuss possible ways to break the cycle. Please see later in the article for the Editors' Summar

Quantifying Bias in Measuring Insecticide-treated Bednet Use: Meta-analysis of Self-reported vs Objectively Measured Adherence

Background Insecticide-treated bednets (ITNs) are recommended for use by 3.4 billion people at risk of malaria world-wide. Policy makers rely on measurements of ITN use to optimize malaria prevention efforts. Self-reports are the most common means of assessing ITN use, but self-reports may be biased in a way that reduces their reliability as a proxy for ITN adherence. This meta-analysis compared self-reported and two methods which are more objective measures of ITN use to explore whether self-reports overestimate actual ITN adherence. Methods A comprehensive search of electronic databases and hand searching reference lists resulted in screening 2885 records and 202 articles were read in full. Sixteen articles with comparable data were chosen for the meta-analysis. Comparable data was defined as self-reported and objectively measured ITN use (observation of a mounted ITN or surprise visits confirming use) at the same unit of analysis, covering the same time period and same population. A random effects model was used to determine a weighted average risk difference between self-reported and objectively measured ITN use. Additional stratified analyses were conducted to explore study heterogeneity. Results Self-reported ITN use is 8 percentage points (95% confidence interval CI: 3 to 13) higher than objectively measured ITN use, representing a 13.6% overestimation relative to the proportion measured as adherent to ITN use by objective measures. Wide variations in the discrepancies between self-reports and objective measures were unable to be explained using stratified analyses of variables including location, year of publication, seasonality and others. Conclusions Self-reports overestimate ITN adherence relative to objectively measured ITN use by 13.6% and do so in an unpredictable manner that raises questions about the reliability of using self-reported ITN use alone as a surveillance tool and a guide for making policy decisions

Adherence to Antiretroviral Treatment and Correlation with Risk of Hospitalization among Commercially Insured HIV Patients in the United States

Purpose: A lower daily pill burden may improve adherence to antiretroviral treatment (ART) and clinical outcomes in patients with human immunodeficiency virus (HIV). This study assessed differences in adherence using the number of pills taken per day, and evaluated how adherence correlated with hospitalization. Methodology: Commercially insured patients in the LifeLink database with an HIV diagnosis (International Classification of Diseases, 9th Revision, Clinical Modification code 042.xx) between 6/1/2006 and 12/31/2008 and receipt of a complete ART regimen were selected for inclusion. Patients were grouped according to their daily pill count and remained on ART for at least 60 days. Outcomes included adherence and rates of hospitalization. Adherence was measured as the proportion of days between the start and end of the regimen in which the patient maintained supply of all initiated ART components. Logistic regressions assessed the relationship between pills per day, adherence, and hospitalization, controlling for demographics, comorbidities, and ART-naïve (vs. experienced) status. Results: 7,073 patients met the study inclusion criteria, and 33.4%, 5.8%, and 60.8 % received an ART regimen comprising one, two, or three or more pills per day, respectively. Regression analysis showed patients receiving a single pill per day were significantly more likely to reach a 95 % adherence threshold versus patients receiving three or more pills per day (odds ratio [OR] = 1.59; P,0.001). Regardless of the number of pills received per day, patients were over 40 % less likely to have

The Risk of Virologic Failure Decreases with Duration of HIV Suppression, at Greater than 50% Adherence to Antiretroviral Therapy

Background: We hypothesized that the percent adherence to antiretroviral therapy necessary to maintain HIV suppression would decrease with longer duration of viral suppression. Methodology: Eligible participants were identified from the REACH cohort of marginally housed HIV infected adults in San Francisco. Adherence to antiretroviral therapy was measured through pill counts obtained at unannounced visits by research staff to each participant's usual place of residence. Marginal structural models and targeted maximum likelihood estimation methodologies were used to determine the effect of adherence to antiretroviral therapy on the probability of virologic failure during early and late viral suppression. Principal Findings: A total of 221 subjects were studied (median age 44.1 years; median CD4+ T cell nadir 206 cells/mm3). Most subjects were taking the following types of antiretroviral regimens: non-nucleoside reverse transcriptase inhibitor based (37%), ritonavir boosted protease inhibitor based (28%), or unboosted protease inhibitor based (25%). Comparing the probability of failure just after achieving suppression vs. after 12 consecutive months of suppression, there was a statistically significant decrease in the probability of virologic failure for each range of adherence proportions we considered, as long as adherence was greater than 50%. The estimated risk difference, comparing the probability of virologic failure after 1 month vs. after 12 months of continuous viral suppression was 0.47 (95% CI 0.23–0.63) at 50–74% adherence, 0.29 (CI 0.03–0.50) at 75–89% adherence, and 0.36 (CI 0.23–0.48) at 90–100% adherence. Conclusions: The risk of virologic failure for adherence greater than 50% declines with longer duration of continuous suppression. While high adherence is required to maximize the probability of durable viral suppression, the range of adherence capable of sustaining viral suppression is wider after prolonged periods of viral suppression

Trauma history and depression predict incomplete adherence to antiretroviral therapies in a low income country.

As antiretroviral therapy (ART) for HIV becomes increasingly available in low and middle income countries (LMICs), understanding reasons for lack of adherence is critical to stemming the tide of infections and improving health. Understanding the effect of psychosocial experiences and mental health symptomatology on ART adherence can help maximize the benefit of expanded ART programs by indicating types of services, which could be offered in combination with HIV care. The Coping with HIV/AIDS in Tanzania (CHAT) study is a longitudinal cohort study in the Kilimanjaro Region that included randomly selected HIV-infected (HIV+) participants from two local hospital-based HIV clinics and four free-standing voluntary HIV counselling and testing sites. Baseline data were collected in 2008 and 2009; this paper used data from 36 month follow-up interviews (N = 468). Regression analyses were used to predict factors associated with incomplete self-reported adherence to ART. INCOMPLETE ART ADHERENCE WAS SIGNIFICANTLY MORE LIKELY TO BE REPORTED AMONGST PARTICIPANTS WHO EXPERIENCED A GREATER NUMBER OF CHILDHOOD TRAUMATIC EVENTS: sexual abuse prior to puberty and the death in childhood of an immediate family member not from suicide or homicide were significantly more likely in the non-adherent group and other negative childhood events trended toward being more likely. Those with incomplete adherence had higher depressive symptom severity and post-traumatic stress disorder (PTSD). In multivariable analyses, childhood trauma, depression, and financial sacrifice remained associated with incomplete adherence.\ud This is the first study to examine the effect of childhood trauma, depression and PTSD on HIV medication adherence in a low income country facing a significant burden of HIV. Allocating spending on HIV/AIDS toward integrating mental health services with HIV care is essential to the creation of systems that enhance medication adherence and maximize the potential of expanded antiretroviral access to improve health and reduce new infections

Diagnosing Bias in the Inverse Probability of Treatment Weighted Estimator Resulting from Violation of Experimental Treatment Assignment

Inverse probability of treatment weighting (IPTW) is frequently used to estimate the causal effects of treatments and interventions. The consistency of the IPTW estimator relies not only on the well-recognized assumption of no unmeasured confounders (Sequential Randomization Assumption or SRA), but also on the assumption of experimentation in the assignment of treatment (Experimental Treatment Assignment or ETA). In finite samples, violations in the ETA assumption can occur due simply to chance; certain treatments become rare or non-existent for certain strata of the population. Such practical violations of the ETA assumption occur frequently in real data, and can result in significant bias in the IPTW estimator of causal effects. This manuscript presents a diagnostic tool for assessing the bias in the IPTW estimator due to violation of the ETA assumption. The Diagnostic of ETA Bias (DEB), implemented in a public R routine, relies on parametric bootstrap sampling from an estimated data-generating distribution. The article presents results of simulations to assess the performance and applications of the diagnostic and to investigate the extent of ETA bias in a range of contexts. In addition, results are presented from two data examples drawn from the treatment of HIV infection, in which DEB is used to assess the ETA bias of the IPTW estimator