The effect of tuberculosis treatment on virologic and CD4+ cell count response to combination antiretroviral therapy

Objective To determine the impact of tuberculosis (TB) treatment at the time of combination antiretroviral therapy (cART) initiation on virologic and CD4 cell count response to cART. Methods Systematic review and meta-analysis of studies reporting HIV RNA and CD4 cell count response, stratified by TB treatment status at cART initiation. Stratified random-effects and meta-regression analyses were used when possible. Results Twenty-five eligible cohort studies reported data on 49 578 (range 42-15 646) adults, of whom 8826 (18%) were receiving TB treatment at cART initiation. Seventeen studies reported virologic response; 21 reported CD4 cell count response. The summarized random-effects relative risk (RRRE) of virologic suppression in those receiving vs. not receiving TB treatment at different time points following cART initiation was 1.06 (0.86-1.29) at 1-4 months, 0.91 (0.83-1.00) at 6 months, 0.99 (0.94-1.05) at 11-12 months, and 0.99 (0.77-1.28) at 18-48 months. The overall RRRE at 1-48 months was 0.97 (95% confidence interval 0.92-1.03). Available data regarding the effect of TB treatment on virologic failure were heterogeneous and inconclusive (13 estimates). Differences in median CD4 cell count gain between those receiving vs. not receiving TB treatment ranged from -10 to 60 cells/μl (median 27) by 6 months (seven estimates) and -10 to 29 (median 6) by 11-12 months (five estimates), although the heterogeneity of the response measures did not support meta-analysis. Conclusion Patients receiving TB treatment at cART initiation experience similar virologic suppression and CD4 cell count reconstitution as those not receiving TB treatment, reinforcing the need to start cART during TB treatment and allowing more confidence in clinical decision-making.