Rifapentine-isoniazid versus isoniazid-alone therapy for tuberculosis prevention among people living with HIV (PLHIV): a systematic review and meta-analysis of randomized trials

Tuberculosis (TB), a substantial cause of morbidity and mortality among people living with human immunodeficiency virus (PLHIV), accounted for 161,000 deaths among HIV-co-infected patients in 2023. Tuberculosis preventive therapy can play a detrimental role in reducing the global burden. However, prolonged treatment duration compromises adherence and ultimately efficacy. This systematic review and meta-analysis aimed to assess the treatment adherence and effectiveness of rifapentine-isoniazid prevention therapy relative to the standard isoniazid therapy. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive literature search was conducted over PubMed/Medline, Google Scholar, Cochrane Library, and Clinicaltrials.gov from inception till 28 October 2024. Recruited articles were screened against the predefined inclusion criteria, and relevant data was extracted into a spreadsheet. Comprehensive Meta-Analysis (CMA) was used for data synthesis. This meta-analysis included four studies containing data from 8,068 patients, with 5640 randomized to the rifapentine-isoniazid group while 2428 received isoniazid alone. Tuberculosis incidence varied from 0.39 to 2.0 and 0.67 to 1.9 per 100 person-years in the rifapentine-isoniazid arm and the isoniazid alone group, respectively. However, the pooled analysis showed a non-significant difference between the two groups (Rate Ratio = 0.849; Confidence Interval = 0.478–1.509; p = 0.578). Similarly, no significant difference was noted across deaths in each group (Odds Ratio = 0.745; Confidence Interval = 0.462–1.201; p = 0.227). While the two preventive therapies were not significantly different in terms of effectiveness, a significant improvement in treatment completion (Odds Ratio = 5.145, Confidence Interval = 2.955–8.957; p < 0.001) and discontinuation due to adverse events (Odds Ratio = 0.515; Confidence Interval = 0.363–0.731; p < 0.001) was observed with the rifapentine-isoniazid group. This study demonstrated no significant differences between short-term rifapentine-isoniazid and isoniazid-alone therapy in reducing active TB cases and deaths. However, an improvement in treatment completion and treatment discontinuation due to adverse events was noted with the former. Not applicable.