Effectiveness of Early Antiretroviral Therapy Initiation to Improve Survival among HIV-Infected Adults with Tuberculosis: A Retrospective Cohort Study

Background: Randomized clinical trials examining the optimal time to initiate combination antiretroviral therapy (cART) in HIV-infected adults with sputum smear-positive tuberculosis (TB) disease have demonstrated improved survival among those who initiate cART earlier during TB treatment. Since these trials incorporated rigorous diagnostic criteria, it is unclear whether these results are generalizable to the vast majority of HIV-infected patients with TB, for whom standard diagnostic tools are unavailable. We aimed to examine whether early cART initiation improved survival among HIV-infected adults who were diagnosed with TB in a clinical setting. Methods and Findings: We retrospectively reviewed charts for 308 HIV-infected adults in Rwanda with a CD4 count#350 cells/ml and a TB diagnosis. We estimated the effect of cART on survival using marginal structural models and simulated 2-y survival curves for the cohort under different cART strategies:start cART 15, 30, 60, or 180 d after TB treatment or never start cART. We conducted secondary analyses with composite endpoints of (1) death, default, or lost to follow-up and (2) death, hospitalization, or serious opportunistic infection. Early cART initiation led to a survival benefit that was most marked for individuals with low CD4 counts. For individuals with CD4 counts of 50 or 100 cells/ml, cART initiation at day 15 yielded 2-y survival probabilities of 0.82 (95 % confidence interval: [0.76, 0.89]) and 0.86 (95 % confidence interval: [0.80, 0.92])