The Effectiveness of Rifapentine-Isoniazid in the Prevention of Tuberculosis Among HIV Infected Patients: A Systematic Review and Meta-analysis of Non-inferiority Randomized Trials

Abstract Introduction: Tuberculosis (TB), a substantial cause of morbidity and mortality among human immunodeficiency virus (HIV) infected individuals, 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 was conducted following the 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. Tuberculosis incidence varied from 0.21 to 2.0 and 0.63 to 1.9 per 100 person-years in the rifapentine-isoniazid arm and isoniazid alone group respectively. However, the pooled analysis showed a non-significant difference between the two groups (OR: 1.12; CI: 0.65 to 1.93; p=0.69) as shown in Figure 1. Similarly, no significant difference was noted across deaths in each group (OR: 0.76; CI: 0.43 to 1.34; p=0.35). While the two preventive therapies were non-inferior in terms of effectiveness, a significant improvement in treatment completion was observed with the rifapentine-isoniazid group (OR: 5.14; CI: 2.96 to 8.96; p<0.0001). Conclusion: The short-term rifapentine-isoniazid preventive therapy was non-inferior to the standard isoniazid therapy, however, a marked improvement in treatment completion was noted with the former.