Protocol for the 3HP Options Trial: a hybrid type 3 implementation-effectiveness randomized trial of delivery strategies for short-course tuberculosis preventive therapy among people living with HIV in Uganda

Kadota, Jillian L.; Musinguzi, Allan; Nabunje, Juliet; Welishe, Fred; Ssemata, Jackie; Opira, Bishop; Berger, Christopher; Patel, Devika; Sammann, Amanda; Katahoire, Anne; Nahid, Payam; Belknap, Robert; Phillips, Patrick; Namusobya, Jennifer; Kamya, Moses R.; Handley, Margaret A.; Kiwanuka, Noah; Katamba, Achilles; Dowdy, David W.; Semitala, Fred C.; Cattamanchi, Adithya

doi:10.1186/s13012-020-01025-8

Cited by 15 publications

(19 citation statements)

References 31 publications

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“…Details of the trial design-including full eligibility criteria-have been published previously [14]. Briefly, the trial included adults (age �18 years) living with HIV engaged in care at the Mulago ISS clinic.…”

Section: Study Design and Participantsmentioning

confidence: 99%

“…The trial protocol paper provides full details of the components of the 3 delivery strategies: facilitated DOT, facilitated SAT, and patient choice between facilitated DOT and facilitated SAT (with the assistance of a decision aid) [14]. Briefly, all strategies included (a) standardized patient counseling about the risks and benefits of 3HP; (b) streamlined clinic visits (11 visits for DOT and 2 for SAT) at the pharmacy window for symptom-based TB screening and side effects screening using a standardized checklist (S1 Text); (c) reimbursement of transport costs for clinic visits; and (d) automated interactive voice response (IVR) reminders for clinic visits.…”

Section: Randomization and Interventionsmentioning

confidence: 99%

“…Research staff screened PLHIV for eligibility, obtained informed consent from eligible participants, administered a baseline demographic and clinical survey, and performed randomization. Participants were then transferred to routine healthcare providers who performed all activities related to 3HP counseling, AE monitoring, dosing and adherence monitoring, and follow-up [14]. Healthcare providers did not receive any incentives or payments for delivering care related to 3HP.…”

Section: Assessments and Data Collectionmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Study Design and Participantsmentioning

confidence: 99%

Section: Randomization and Interventionsmentioning

confidence: 99%

Section: Assessments and Data Collectionmentioning

confidence: 99%

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

et al. 2021

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“…We are now conducting a randomized trial of different patient-centered treatment support approaches (directly observed therapy, self-administered therapy, or informed choice) to add empirical, quantitative findings to this body of evidence [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…The aim of this qualitative study was to identify potential barriers to, and facilitators of, 3HP acceptance and completion, from the perspective of PLHIV in HIV/AIDS care and health workers at a large, urban HIV/AIDS clinic in Kampala, Uganda, and map these onto the COM-B model and BCW framework to identify suitable intervention functions. The goal was to inform the design of SAT and DOT delivery strategies for a type 3 hybrid effectiveness-implementation trial of 3HP [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Acceptance and completion of rifapentine-based TB preventive therapy (3HP) among people living with HIV (PLHIV) in Kampala, Uganda—patient and health worker perspectives

Semitala

Musinguzi

Ssemata

et al. 2021

Implement Sci Commun

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Background A 12-dose, once-weekly regimen of isoniazid and rifapentine (3HP) is effective in preventing tuberculosis (TB) among people living with HIV (PLHIV). We sought to identify potential barriers to and facilitators of acceptance and completion of 3HP treatment from the perspective of people living with HIV (PLHIV) and health workers in a routine HIV care setting in Kampala, Uganda. Methods We conducted semi-structured interviews with 25 PLHIV and 10 health workers at an HIV/AIDS clinic in Kampala, Uganda. For both groups, we explored their understanding and interpretations of TB and TB preventive therapy (TPT), and perceptions about social and contextual factors that might influence the willingness of PLHIV to initiate and complete 3HP. We analyzed the data using an inductive thematic approach and aligned the emergent themes to the Behavior Change Wheel framework to identify sources of behavior and targeted behavior change interventions. Results Facilitators of acceptance and completion of 3HP treatment among PLHIV were fear of contracting TB, awareness of being at risk of getting TB, willingness to take TPT, trust in health workers, and the perceived benefits of directly observed therapy (DOT) and self-administered therapy (SAT) 3HP delivery strategies. Barriers included inadequate understanding of TPT, fear of potential side effects, concerns about the effectiveness of 3HP, and the perceived challenges of DOT or SAT. Among health workers, perceived facilitators included knowledge that TB is a common cause of mortality for PLHIV, fear of getting TB, and trust in the health workers by PLHIV, the advantages of once-weekly 3HP dosing, and the benefits of DOT and SAT 3HP delivery strategies. Health worker-reported barriers for PLHIV included inadequate understanding of TB and benefits of TPT, TB-associated stigma, potential side effects pill burden, and challenges of DOT and SAT 3HP delivery strategies. Lack of experience in the use of digital technology to monitor patient care was identified as a health worker-specific barrier. Identified intervention functions to address the facilitators or barriers included education, persuasion, environmental restructuring, enablement, and training. Conclusions Using a formative qualitative and comprehensive theoretical approach, we identified key barriers, facilitators, and appropriate interventions, including patient education, enhancing trust, and patient-centered treatment support that could be used to optimize the delivery of 3HP to PLHIV in our setting. These interventions are likely generalizable to other clinical interventions in similar populations in sub-Saharan Africa and other TB high-burden settings.

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Preferences of people living with HIV for features of tuberculosis preventive treatment regimens in Uganda: a discrete choice experiment

Aschmann,

Musinguzi,

Kadota

et al. 2024

J Int AIDS Soc.

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IntroductionTuberculosis (TB) preventive treatment (TPT) is recommended for people living with HIV (PLHIV) in high TB burden settings. While 6 months of daily isoniazid remains widely used, shorter regimens are now available. However, little is known about preferences of PLHIV for key features of TPT regimens.MethodsFrom July to November 2022, we conducted a discrete choice experiment among adult PLHIV engaged in care at an urban HIV clinic in Kampala, Uganda. Participants chose between two hypothetical TPT regimens with five different features (pills per dose, frequency, duration, need for adjusted antiretroviral therapy [ART] dosage and side effects), organized across nine random choice tasks. We analysed preferences using hierarchical Bayesian estimation, latent class analysis and willingness‐to‐trade simulations.ResultsOf 400 PLHIV, 392 (median age 44, 72% female, 91% TPT‐experienced) had high‐quality choice task responses. Pills per dose was the most important attribute (relative importance 32.4%, 95% confidence interval [CI] 31.6–33.2), followed by frequency (20.5% [95% CI 19.7–21.3]), duration (19.5% [95% CI 18.6–20.5]) and need for ART dosage adjustment (18.2% [95% CI 17.2–19.2]). Latent class analysis identified three preference groups: one prioritized less frequent, weekly dosing (N = 222; 57%); another was averse to ART dosage adjustment (N = 107; 27%); and the last prioritized short regimens with fewer side effects (N = 63; 16%). All groups highly valued fewer pills per dose. Overall, participants were willing to accept a regimen of 2.8 months’ additional duration [95% CI: 2.4–3.2] to reduce pills per dose from five to one, 3.6 [95% CI 2.4–4.8] months for weekly rather than daily dosing and 2.2 [95% CI 1.3–3.0] months to avoid ART dosage adjustment.ConclusionsTo align with preferences of PLHIV in Uganda, decision‐makers should prioritize the development and implementation of TPT regimens with fewer pills, less frequent dosing and no need for ART dosage adjustment, rather than focus primarily on duration of treatment.

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Protocol for the 3HP Options Trial: a hybrid type 3 implementation-effectiveness randomized trial of delivery strategies for short-course tuberculosis preventive therapy among people living with HIV in Uganda

Cited by 15 publications

References 31 publications

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

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

Acceptance and completion of rifapentine-based TB preventive therapy (3HP) among people living with HIV (PLHIV) in Kampala, Uganda—patient and health worker perspectives

Preferences of people living with HIV for features of tuberculosis preventive treatment regimens in Uganda: a discrete choice experiment

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