Tuberculosis preventive therapy for people living with HIV: A systematic review and network meta-analysis

Tuberculosis (TB) preventive therapy (TPT) is an essential component of care for people living with HIV (PLHIV). We compared efficacy, safety, completion, and drug-resistant TB risk for currently recommended TPT regimens through a systematic review and network meta-analysis (NMA) of randomized trials. We searched MEDLINE, Embase, and the Cochrane Library from inception through June 9, 2020 for randomized controlled trials (RCTs) comparing 2 or more TPT regimens (or placebo/no treatment) in PLHIV. Two independent reviewers evaluated eligibility, extracted data, and assessed the risk of bias. We grouped TPT strategies as follows: placebo/no treatment, 6 to 12 months of isoniazid, 24 to 72 months of isoniazid, and rifamycin-containing regimens. A frequentist NMA (using graph theory) was carried out for the outcomes of development of TB disease, all-cause mortality, and grade 3 or worse hepatotoxicity. For other outcomes, graphical descriptions or traditional pairwise meta-analyses were carried out as appropriate. The potential role of confounding variables for TB disease and all-cause mortality was assessed through stratified analyses. Rifamycin-containing regimens appear safer and at least as effective as isoniazid regimens in preventing TB and death and should be considered part of routine care in PLHIV. Knowledge gaps remain as to which specific rifamycin-containing regimen provides the optimal balance of efficacy, completion, and safety.