The Effect of Tuberculosis Treatment at Combination Antiretroviral Therapy Initiation on Subsequent Mortality: A Systematic Review and Meta-Analysis

OBJECTIVE: We aimed to perform a systematic review and meta-analysis examining the impact of TB treatment at the time of combination antiretroviral therapy (cART) initiation on subsequent mortality. METHODS: We searched PubMed, EMBASE, and selected conference proceedings for studies that report adult mortality on cART, stratified by TB treatment status at cART initiation. Stratified random-effects and meta-regression analyses were used to examine the influence of study and population characteristics. RESULTS: 22 eligible cohort studies reported data on 98,350 (range 74-15,225) adults, of whom 14,779 (15%) were receiving TB treatment at cART initiation. Studies of those receiving vs. not receiving TB treatment had an average mortality relative risk of 1.10 (95% confidence interval 0.87-1.40) at 1-3 months (based upon 8 estimates), 1.15 (0.94-1.41) at 6-12 months (11 estimates), and 1.33 (1.02-1.75) at 18-98 months (10 estimates) following cART initiation. However, there was a wide range of estimates and those at later time points were markedly heterogeneous. Meta-regression identified factors associated with elevated average risk estimates: lower median baseline CD4 counts and adjustment for baseline hemoglobin at 1-3 months; longer length of follow-up and women-only studies at 6-12 months; and not adjusting for BMI/weight at 18-98 months. CONCLUSIONS: Patients receiving TB treatment at cART initiation did not have a statistically significant estimated increase in short-term risk of all-cause mortality as compared to those not receiving TB treatment. TB treatment was significantly associated with increased mortality after about a year of cART, suggesting that patients with concurrent TB treatment at cART initiation may benefit from continued support after TB treatment completion.