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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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 Ratioƒ_%=ƒ_%0.849; Confidence Intervalƒ_%=ƒ_%0.478ƒ_”1.509; pƒ_%=ƒ_%0.578). Similarly, no significant difference was noted across deaths in each group (Odds Ratioƒ_%=ƒ_%0.745; Confidence Intervalƒ_%=ƒ_%0.462ƒ_”1.201; pƒ_%=ƒ_%0.227). While the two preventive therapies were not significantly different in terms of effectiveness, a significant improvement in treatment completion (Odds Ratioƒ_%=ƒ_%5.145, Confidence Intervalƒ_%=ƒ_%2.955ƒ_”8.957; pƒ_%<ƒ_%0.001) and discontinuation due to adverse events (Odds Ratioƒ_%=ƒ_%0.515; Confidence Intervalƒ_%=ƒ_%0.363ƒ_"0.731; pƒ_%<ƒ_%0.001) was observed with the rifapentine-isoniazid group. CONCLUSION: 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. CLINICAL TRIAL NUMBER: Not applicable. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-025-12412-1

• Population(s)
  • General HIV+ population
• Co-infections
  • Tuberculosis
• Health Systems
  • Governance arrangements