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Background Mortality among adults with human immunodeficiency virus (HIV) remains elevated over those in the US general population, even in the years after entry into HIV care. We explore whether the elevation in 5-year mortality would have persisted if all adults with HIV had initiated antiretroviral therapy within 3 months of entering care. Methods Among 82 766 adults entering HIV care at North American AIDS Cohort Collaboration clinical sites in the United States, we computed mortality over 5 years since entry into HIV care under observed treatment patterns. We then used inverse probability weights to estimate mortality under universal early treatment. To compare mortality with those for similar individuals in the general population, we used National Center for Health Statistics data to construct a cohort representing the subset of the US population matched to study participants on key characteristics. Results For the entire study period (1999–2017), the 5-year mortality among adults with HIV was 7.9% (95% confidence interval [CI]: 7.6%–8.2%) higher than expected based on the US general population. Under universal early treatment, the elevation in mortality for people with HIV would have been 7.2% (95% CI: 5.8%–8.6%). In the most recent calendar period examined (2011–2017), the elevation in mortality for people with HIV was 2.6% (95% CI: 2.0%–3.3%) under observed treatment patterns and 2.1% (.0%–4.2%) under universal early treatment. Conclusions Expanding early treatment may modestly reduce, but not eliminate, the elevation in mortality for people with HIV. [ABSTRACT FROM AUTHOR]

Background Intention-to-treat comparisons of randomized trials provide asymptotically consistent estimators of the effect of treatment assignment, without regard to compliance. However, decision makers often wish to know the effect of a per-protocol comparison. Moreover, decision makers may also wish to know the effect of treatment assignment or treatment protocol in a user-specified target population other than the sample in which the trial was fielded. Here, we aimed to generalize results from the ACTG A5095 trial to the US recently HIV-diagnosed target population. Methods We first replicated the published conventional intention-to-treat estimate (2-year risk difference and hazard ratio) comparing a four-drug antiretroviral regimen to a three-drug regimen in the A5095 trial. We then estimated the intention-to-treat effect that accounted for informative dropout and the per-protocol effect that additionally accounted for protocol deviations by constructing inverse probability weights. Furthermore, we employed inverse odds of sampling weights to generalize both intention-to-treat and per-protocol effects to a target population comprising US individuals with HIV diagnosed during 2008–2014. Results Of 761 subjects in the analysis, 82 dropouts (36 in the three-drug arm and 46 in the four-drug arm) and 59 protocol deviations (25 in the three-drug arm and 34 in the four-drug arm) occurred during the first 2 years of follow-up. A total of 169 subjects incurred virologic failure or death. The 2-year risks were similar both in the trial and in the US HIV-diagnosed target population for estimates from the conventional intention-to-treat, dropout-weighted intention-to-treat, and per-protocol analyses. In the US target population, the 2-year conventional intention-to-treat risk difference (unit: %) for virologic failure or death comparing the four-drug arm to the three-drug arm was −0.4 (95% confidence interval: −6.2, 5.1), while the hazard ratio was 0.97 (95% confidence interval: 0.70, 1.34); the 2-year risk difference was −0.9 (95% confidence interval: −6.9, 5.3) for the dropout-weighted intention-to-treat comparison (hazard ratio = 0.95, 95% confidence interval: 0.68, 1.32) and −0.7 (95% confidence interval: −6.7, 5.5) for the per-protocol comparison (hazard ratio = 0.96, 95% confidence interval: 0.69, 1.34). Conclusion No benefit of four-drug antiretroviral regimen over three-drug regimen was found from the conventional intention-to-treat, dropout-weighted intention-to-treat or per-protocol estimates in the trial sample or target population. [ABSTRACT FROM AUTHOR]

Background Research linking depression to mortality among people living with human immunodeficiency virus (PLWH) has largely focused on binary "always vs never" characterizations of depression. However, depression is chronic and is likely to have cumulative effects on mortality over time. Quantifying depression as a cumulative exposure may provide a better indication of the clinical benefit of enhanced depression treatment protocols delivered in HIV care settings. Methods Women living with HIV (WLWH), naive to antiretroviral therapy, from the Women's Interagency HIV Study were followed from their first visit in or after 1998 for up to 10 semiannual visits (5 years). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale. An area-under-the-curve approach was used to translate CES-D scores into a time-updated measure of cumulative days with depression (CDWD). We estimated the effect of CDWD on all-cause mortality using marginal structural Cox proportional hazards models. Results Overall, 818 women contributed 3292 woman-years over a median of 4.8 years of follow-up, during which the median (interquartile range) CDWD was 366 (97–853). Ninety-four women died during follow-up (2.9 deaths/100 woman-years). A dose–response relationship was observed between CDWD and mortality. Each additional 365 days spent with depression increased mortality risk by 72% (hazard ratio, 1.72; 95% confidence interval, 1.34–2.20). Conclusions In this sample of WLWH, increased CDWD elevated mortality rates in a dose–response fashion. More frequent monitoring and enhanced depression treatment protocols designed to reduce CDWD may interrupt the accumulation of mortality risk among WLWH. [ABSTRACT FROM AUTHOR]