Clinical effectiveness of three months once-weekly Isoniazid and Rifapentine regimen for treatment of Latent TB Infection: a systematic review and meta-analysis

Globally, multiple TB preventive treatment (TPT) regimens are available for Latent Tuberculosis Infection (LTBI) and implementing TPT is essential for achieving TB elimination. Standard treatments for LTBI include 9 and 6-month isoniazid monotherapy (9H and 6H) regimens, recent clinical trials also introduced the shorter once-weekly 3-month isoniazid plus rifapentine (3HP) regimen. To evaluate the clinical effectiveness of 3HP in adults, we performed a comprehensive synthesis on the clinical effectiveness (treatment completion, adverse drug reactions (ADRs) and exploratory analysis of incident active TB) of the 3HP regimen compared with 9H and 6H. A systematic search was carried out in PubMed, EMBASE, ScienceDirect, and Cochrane Library. An excel data collection tool was used for collecting the required data. Pooled estimates of effectiveness were calculated through random-effects meta-analysis model using odds ratio (OR) and risk ratio (RR) as summary measures. Risk of bias was assessed using the RoB 2.0 and ROBINS-I tools, and publication bias was evaluated. The certainty of the evidence was assessed using the GRADE approach. Twenty studies met eligibility criteria, of which 5 were trials and 15 were observational studies. Meta-analysis showed that participants receiving the 3HP regimen were nearly three times more likely to complete treatment compared to 9H regimen (OR = 2.81; 95% CI: 2.05–3.86; low certainty) and the OR was 2.91 compared to 6H regimen. The risk of ADRs was 1% higher with 3HP when compared to 9H (RR = 1.01; 95% CI: 0.76–1.33; very low certainty). The pooled RR of adverse events, such as grade 1–2, grade 3–4, grade 5 and hepatotoxicity were 1.38 (95% CI: 0.73–2.59; I 2 = 75.9%), 1.19 (95% CI: 0.78–1.82; I 2 = 16.6%), 0.77 (95% CI: 0.49–1.22; I 2 = 0%) and 0.26 (95% CI: 0.18–0.38; I 2 = 17.7%) respectively. Exploratory analysis suggested a lower incidence of active TB with 3HP compared to 9H; however, the difference was not statistically significant (RR = 0.47; 95% CI: 0.16–1.38; moderate certainty). The shorter 3HP regimen is associated with higher treatment completion and lower hepatotoxicity compared to 9H, with evidence on progression to active TB remains exploratory and imprecise. Limited evidence on 6H showed improved treatment completion with 3HP. These findings should be interpreted cautiously as most evidence was derived from heterogeneous observational studies, and the certainty of evidence for main outcomes was low to very low. Not applicable.