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 combinationantiretroviral therapy (cART) in HIV-infected adults with sputumsmear-positive tuberculosis (TB) disease have demonstrated improved survivalamong those who initiate cART earlier during TB treatment. Since thesetrials incorporated rigorous diagnostic criteria, it is unclear whetherthese results are generalizable to the vast majority of HIV-infectedpatients with TB, for whom standard diagnostic tools are unavailable. Weaimed to examine whether early cART initiation improved survival amongHIV-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 witha CD4 count≤350 cells/µl and a TB diagnosis. We estimated theeffect of cART on survival using marginal structural models and simulated2-y survival curves for the cohort under different cART strategies:startcART 15, 30, 60, or 180 d after TB treatment or never start cART. Weconducted secondary analyses with composite endpoints of (1) death, default,or lost to follow-up and (2) death, hospitalization, or seriousopportunistic infection. Early cART initiation led to a survival benefitthat was most marked for individuals with low CD4 counts. For individualswith CD4 counts of 50 or 100 cells/µl, cART initiation at day 15yielded 2-y survival probabilities of 0.82 (95% confidence interval:[0.76, 0.89]) and 0.86 (95% confidence interval:[0.80, 0.92]), respectively. These were significantly higher thanthe probabilities computed under later start times. Results were similar forthe endpoint of death, hospitalization, or serious opportunistic infection.cART initiation at day 15 versus later times was protective against death,default, or loss to follow-up, regardless of CD4 count. As with anyobservational study, the validity of these findings assumes that biases fromresidual confounding by unmeasured factors and from model misspecificationare small.

Conclusions

Early cART reduced mortality among individuals with low CD4 counts andimproved retention in care, regardless of CD4 count.Please see later in the article for the Editors'' Summary