The effect of tuberculosis treatment at the time of combination antiretroviral therapy (cART) initiation on response to cART among HIV-infected individuals

Given the World Health Organization's 2010 recommendation that all HIV-infected persons with tuberculosis (TB) be initiated on combination antiretroviral therapy (cART), regardless of CD4 count, many individuals will be initiating cART while concurrently on TB treatment. Co-treated individuals may experience a differential response to cART due to drug-drug interactions, increased risk of drug toxicity, immune reconstitution inflammatory syndrome, and potentially lower adherence due to the high pill burden. The effect of TB treatment on a patient's response to cART is not yet clear and requires careful evaluation. Systematic reviews and meta-analytic methods examined the effect of TB treatment at the time of cART initiation on mortality and virologic and CD4 count response to cART among adults. A secondary analysis of South African study data assessed the effect of TB treatment on virologic and immunologic response to cART among children. Adults receiving vs. not receiving TB treatment at cART initiation had a mortality relative risk of 1.10 (95% confidence interval 0.87-1.40) at 1-3 months, 1.15 (0.94-1.41) at 6-12 months, and 1.33 (1.02-1.75) at 18-98 months following cART initiation. TB treatment did not influence the risk of virologic suppression at any time point from 1-48 months following cART initiation. Differences in median CD4 count gain between those receiving vs. not receiving TB treatment ranged from -10 to 60 cells/μL (median 27) by 6 months and -10 to 29 (median 6) by 11-12 months. Among 199 children initiating cART (median age 2.1 years), TB treatment was not associated with time to virologic suppression (adjusted hazard ratio [aHR] 1.36 [0.94-1.96]) or virologic rebound (23% vs. 24%, aHR 1.53 [0.71-3.30]). Those receiving TB treatment had lower median CD4 cell percentage (CD4%) until 12 months, but similar median increases in CD4% as children not receiving TB treatment over 24 months of follow-up. TB treatment may be associated with increased adult mortality after a year of cART, but was not associated with virologic or immunologic response to cART in adults or children, suggesting that patients receiving concurrent TB treatment at cART initiation may not have an inferior response to cART.