Efficacy, safety, and tolerability of isoniazid preventive therapy for tuberculosis in people living with HIV

Objective: The aim of this study was to systematically assess the efficacy, safety, and tolerability of isoniazid preventive therapy (IPT) for tuberculosis (TB) in people with HIV (PWH).Design:A systematic review and meta-analysis. Methods: A thorough literature search was performed using PubMed, Cochrane CENTRAL, and Google Scholar from their inception to June 30, 2021. All randomized controlled trials (RCTs) investigating the efficacy, safety, or tolerability of IPT on PWH compared with placebo or active comparators were included in the study. The heterogeneity among the studies was identified by using the I-2 statistic and Cochran's Q test. Results: Out of the 924 nonduplicate RCTs identified through database searching and other sources, 26 studies comprising 38005 patients were included. The overall effect estimate identified the reduction of active TB incidence [odds ratio (OR) 0.69; 95% confidence interval (95% CI) 0.57-0.84; P<0.001], but not all-cause mortality (OR 0.91; 95% CI 0.82, 1.02; P=0.10) with IPT compared with the control. In addition, no significant association was identified between the use of IPT and the risk of peripheral neuropathy (OR 1.50; 95% CI 0.96-2.36; P=0.08) and hepatotoxicity (OR 1.21; 95% CI 0.97-1.52; P=0.09). Conclusion: This systematic review and meta-analysis identified a significant reduction in the incidence of active TB, but not all-cause mortality, among PWH who received IPT compared with the control. Lesser number of outcomes may be the reason for nonsignificant results in terms of safety outcomes of IPT. Therefore, there is a need for extensive and long-term studies to address these issues further, especially in TB/HIV endemic areas.