Psychosocial Predictors of Non-Adherence and Treatment Failure in a Large Scale Multi-National Trial of Antiretroviral Therapy for HIV: Data from the ACTG A5175/PEARLS Trial

Background: PEARLS, a large scale trial of antiretroviral therapy (ART) for HIV (n = 1,571, 9 countries, 4 continents), found that a once-daily protease inhibitor (PI) based regimen (ATV+DDI+FTC), but not a once-daily non-nucleoside reverse transcriptase inhibitor/nucleoside reverse transcriptase inhibitor (NNRTI/NRTI) regimen (EFV+FTC/TDF), had inferior efficacy compared to a standard of care twice-daily NNRTI/NRTI regimen (EFV+3TC/ZDV). The present study examined non-adherence in PEARLS. Methods: Outcomes: non-adherence assessed by pill count and by self-report, and time to treatment failure. Longitudinal predictors: regimen, quality of life (general health perceptions = QOL-health, mental health = QOL-mental health), social support, substance use, binge drinking, and sexual behaviors. “Life-Steps” adherence counseling was provided. Results: In both pill-count and self-report multivariable models, both once-a-day regimens had lower levels of non-adherence than the twice-a-day standard of care regimen; although these associations attenuated with time in the self-report model. In both multivariable models, hard-drug use was associated with non-adherence, living in Africa and better QOL-health were associated with less non-adherence. According to pill-count, unprotected sex was associated with non-adherence. According to self-report, soft-drug use was associated with non-adherence and living in Asia was associated with less non-adherence. Both pill-count (HR = 1.55, 95% CI: 1.15, 2.09, p<.01) and self-report (HR = 1.13, 95% CI: 1.08, 1.13, p<.01) non-adherence were significant predictors of treatment failure over 72 weeks. In multivariable models (including pill-count or self-report nonadherence), worse QOL-health, age group (younger), and region were also significant predictors of treatment failure. Conclusion: In the context of a large, multi-national, multi-continent, clinical trial there were variations in adherence over time, with more simplified regimens generally being associated with better adherence. Additionally, variables such as QOL-health, regimen, drug-use, and region play a role. Self-report and pill-count adherence, as well as additional psychosocial variables, such QOL-health, age, and region, were, in turn, associated with treatment failure

Human Immunodeficiency Virus Type 1 and Tuberculosis Coinfection in Multinational, Resource-limited Settings: Increased Neurological Dysfunction.

BACKGROUND:AIDS Clinical Trial Group 5199 compared neurological and neuropsychological test performance of human immunodeficiency virus type 1 (HIV-1)-infected participants in resource-limited settings treated with 3 World Health Organization-recommended antiretroviral (ART) regimens. We investigated the impact of tuberculosis (TB) on neurological and neuropsychological outcomes. METHODS:Standardized neurological and neuropsychological examinations were administered every 24 weeks. Generalized estimating equation models assessed the association between TB and neurological/neuropsychological performance. RESULTS:Characteristics of the 860 participants at baseline were as follows: 53% female, 49% African; median age, 34 years; CD4 count, 173 cells/μL; and plasma HIV-1 RNA, 5.0 log copies/mL. At baseline, there were 36 cases of pulmonary, 9 cases of extrapulmonary, and 1 case of central nervous system (CNS) TB. Over the 192 weeks of follow-up, there were 55 observations of pulmonary TB in 52 persons, 26 observations of extrapulmonary TB in 25 persons, and 3 observations of CNS TB in 2 persons. Prevalence of TB decreased with ART initiation and follow-up. Those with TB coinfection had significantly poorer performance on grooved pegboard (P &lt; .001) and fingertapping nondominant hand (P &lt; .01). TB was associated with diffuse CNS disease (P &lt; .05). Furthermore, those with TB had 9.27 times (P &lt; .001) higher odds of reporting decreased quality of life, and had 8.02 times (P = .0005) higher odds of loss of productivity. CONCLUSIONS:TB coinfection was associated with poorer neuropsychological functioning, particularly the fine motor skills, and had a substantial impact on functional ability and quality of life. CLINICAL TRIALS REGISTRATION:NCT00096824

Risk Factors of Time to Treatment Failure.

1<p>All adjusted models include treatment condition.</p><p>Table Legend:</p><p>QOL_health: general health perceptions.</p><p>QOL_mental: mental health.</p

Baseline Participant Characteristics.

<p>Table Legend:</p><p>QOL_health: general health perceptions.</p><p>QOL_mental: mental health.</p><p>Treatment: Once daily protease inhibitor + nucleoside reverse transcriptase inhibitors: atazanavir + didanosine-EC and emtricitabine.</p><p>Treatment: Once daily non-nucleoside reverse transcriptase inhibitor + nucleoside reverse transcriptase inhibitors: efavirenz + co-formulated emtricitabine-tenofovir-DF.</p><p>Standard of care: efavirenz plus co-formulated lamivudine-zidovudine.</p

ACTG A5175/Pearls trial – Survival probability estimate from randomization to treatment failure by pill count non-adherence (solid line = did not miss any pills; dashed line = missed any pills).

<p>ACTG A5175/Pearls trial – Survival probability estimate from randomization to treatment failure by pill count non-adherence (solid line  =  did not miss any pills; dashed line  =  missed any pills).</p