Completion of isoniazid–rifapentine (3HP) for tuberculosis prevention among people living with HIV: Interim analysis of a hybrid type 3 effectiveness–implementation randomized trial
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Date
2021
Journal Title
Journal ISSN
Volume Title
Publisher
PLoS Med
Abstract
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
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.
Description
Keywords
Isoniazid–rifapentine (3HP), Tuberculosis prevention, HIV: Interim
Citation
Semitala FC, Kadota JL, Musinguzi A, Nabunje J, Welishe F, Nakitende A, et al. (2021) Completion of isoniazid–rifapentine (3HP) for tuberculosis prevention among people living with HIV: Interim analysis of a hybrid type 3 effectiveness–implementation randomized trial. PLoS Med 18(12): e1003875. https://doi.org/ 10.1371/journal.pmed.1003875