Completion of isoniazid–rifapentine (3HP) for tuberculosis prevention among people living with HIV: Interim analysis of a hybrid type 3 effectiveness–implementation randomized trial

Abstract

Background Scaling up shorter regimens for tuberculosis (TB) prevention such as once weekly isoniazid–rifapentine (3HP) taken for 3 months is a key priority for achieving targets set forth in the World Health Organization’s (WHO) END TB Strategy. However, there are few data on 3HP patient acceptance and completion in the context of routine HIV care in sub-Saharan Africa. Methods and findings The 3HP Options Trial is a pragmatic, parallel type 3 effectiveness–implementation randomized trial comparing 3 optimized strategies for delivering 3HP—facilitated directly observed therapy (DOT), facilitated self-administered therapy (SAT), or informed choice between DOT and SAT using a shared decision-making aid—to people receiving care at a large urban HIV clinic in Kampala, Uganda. Participants and healthcare providers were not blinded to arm assignment due to the nature of the 3HP delivery strategies. We conducted an interim analysis of participants who were enrolled and exited the 3HP treatment period between July 13, 2020 and April 30, 2021. The primary outcome, which was aggregated across trial arms for this interim analysis, was the proportion who accepted and completed 3HP (≥11 of 12 doses within 16 weeks of randomization). We used Bayesian inference analysis to estimate the posterior probability that this proportion would exceed 80% under at least 1 of the 3HP delivery strategies, a coprimary hypothesis of the trial. Through April 2021, 684 participants have been enrolled, and 479 (70%) have exited the treatment period. Of these 479 participants, 309 (65%) were women, mean age was 41.9 years (standard deviation (SD): 9.2), and mean time on antiretroviral therapy (ART) was 7.8 years (SD: 4.3). In total, 445 of them (92.9%, 95% confidence interval (CI): [90.2 to 94.9]) accepted and completed 3HP treatment. There were no differences in treatment acceptance and completion by sex, age, or time on ART. Treatment was discontinued due to a documented adverse event (AE) in 8 (1.7%) patients. The probability that treatment acceptance and completion exceeds 80% under at least 1 of the three 3HP delivery strategies was greater than 99%. The main limitations are that the trial was conducted at a single site, and the interim analysis focused on aggregate outcome data to maintain blinding of investigators to arm-specific outcomes. Conclusions The 3HP was widely accepted by people living with HIV (PLHIV) in Uganda, and very high levels of treatment completion were achieved in a programmatic setting. These findings show that 3HP can enable effective scale-up of tuberculosis preventive therapy (TPT) in high-burden countries, particularly when delivery strategies are tailored to target known barriers to treatment completion. Trial registration ClinicalTrials.gov NCT03934931.

Viral suppression among adults with HIV receiving routine dolutegravir-based antiretroviral therapy and 3 months weekly isoniazid-rifapentine

“…Despite WHO recommendations supporting the global scale-up of 3HP and DTG, there have been some safety concerns stemming from a small study of 3HP and DTG conducted among HIV-negative healthy volunteers that was stopped early after two of four participants experienced adverse events [12]. Our results differ from this study and are consistent with subsequent studies demonstrating the safety of 3HP co-administered with DTG-based ART among PWH [13,16]. As these latter studies were conducted among treatment-experienced PWH with high CD4 þ cell count (median >683 cells/ ml), our trial extends their findings by demonstrating the safety and tolerability of 3HP among ART-naı ¨ve PWH with low CD4 þ cell count (median 188 cells/ml) initiating DTG-based ART, thus supporting its continued global scale-up.…”

Comparison of 3 optimized delivery strategies for completion of isoniazid-rifapentine (3HP) for tuberculosis prevention among people living with HIV in Uganda: A single-center randomized trial

“…Despite its strengths, this study also had some limitations. Although we conducted and reported an interim analysis of the primary outcome aggregated across arms [ 22 ], the minimal difference in the aggregate proportion accepting and completing 3HP in the interim versus final analysis (0.93 versus 0.94, respectively) and the lack of difference between trial arms suggest that the interim analysis did not have a major impact on final trial results. This was a single center trial that excluded people living further than 25 kilometers from the clinic and those who did not own/have access to a phone.…”

Optimizing delivery strategies for 3HP TB preventive treatment in Tanzania: A qualitative study on acceptability of family approach in HIV care and treatment centers

“…The copyright holder for this preprint this version posted April 5, 2024. ; https://doi.org/10.1101/2024.04.04.24305275 doi: medRxiv preprint Overall, many studies have documented 3HP completion to be ≥80%, higher than SAT IPT in varied TB burden countries under research or routine conditions and have assessed varied 3HP delivery strategies such as; direct observed therapy (DOT), video directly observed therapy (VDOT), SAT alone, SAT with text reminders and facilitated SAT with few conditional clinic visits for DOT (11,(13)(14)(15). However, 3HP completion rates vary depending on type of delivery strategy and programmatic setting.…”