Background
Short-course rifapentine-based tuberculosis preventive therapy (TPT), including 1HP (1-month daily isoniazid plus rifapentine) and 3HP (3-month weekly isoniazid plus rifapentine), is recommended for people with HIV (PWH). Data on long-term rifapentine based TPT, safety, and HIV virologic outcomes in high TB-burden Southeast Asian populations are limited.
Methods
We conducted a randomized, open-label, phase 3 noninferiority trial comparing 1HP versus 3HP in PWH across 14 sites in Thailand. The primary endpoint was incidence of tuberculosis or death from any cause. Secondary endpoints included HIV-RNA suppression (<50 copies/mL), adverse events (AEs), serious adverse events (SAEs), hepatotoxicity, hypersensitivity reactions, and treatment discontinuation. Outcomes were analyzed overall and stratified by ART backbone (dolutegravir [DTG] vs. efavirenz [EFV]) and baseline CD4 count (<200 vs. ≥200 cells/µL).
Results
A total of 1,500 PWH without active TB receiving EFV/TDF/FTC or DTG/TDF/3TC were randomized to 1HP (n=748) or 3HP (n=752) and followed for a median of 3.7 (IQR: 2.9-5.1) years. Most participants were male (81.7%) with a median CD4 count of 349 cells/µL (IQR 214–559); 22.6% had CD4 <200 cells/µL. Median ART duration at baseline was 3.5 months (IQR 0.8–50.6), with 58% on EFV-based and 42% on DTG-based ART. The primary endpoint occurred in 5 participants (2 TB, 3 deaths; 0.67%) in the 1HP arm and 3 participants (1 TB, 2 deaths; 0.40%) in the 3HP arm, corresponding to incidence rates were 1.7 (95%CI:0.7-4.1) and 1.0 (95%CI:0.3-3.2) per 1000 person-years, respectively. HIV-RNA suppression was maintained through 144 weeks (96.1% vs. 95.5% for 1HP vs. 3HP, p=0.59), with consistent outcomes across ART regimens and CD4 strata. Grade 3–4 AEs occurred in 2.4% of participants in each arm, SAEs in 1.1% (1HP) versus 0.9% (3HP, p=0.79), hepatotoxicity in 1.5% vs. 1.7%, hypersensitivity in 0.3% vs. 0.5% (p=0.69), and treatment discontinuation in 1.5% vs. 1.3% (p=0.82), with no significant differences between groups.
Conclusions
In PWH on contemporary ART in Thailand, both 1HP and 3HP are highly effective, safe, and well tolerated for TB prevention, maintaining durable HIV virologic suppression. The shorter 1HP regimen provides a convenient alternative to 3HP, supporting its implementation in high TB-burden, HIV-endemic settings.