Options for Delivery of Short-Course Tuberculosis Preventive Therapy: The 3HP Options Trial

Investigator: Adithya Cattamanchi, MD
Sponsor: NIH National Heart, Lung, and Blood Institute

Location(s): Uganda


Tuberculosis (TB) remains the leading cause of death among people living with HIV (PLHIV) but can be prevented with medications, including a recently approved 12-dose regimen. This proposed studies will provide a definitive, comprehensive evaluation of three strategies – including offering patients a personal choice – for delivering this new treatment regimen to PLHIV in a high TB-burden, low-income setting. The results of this trial will inform policy and scale-up, with the ultimate aim of improving the health of PLHIV worldwide.

Isoniazid preventive therapy (IPT) is known to reduce tuberculosis (TB) incidence among people living with HIV (PLHIV) and is considered a core service of National AIDS Programs. Yet, few PLHIV in sub-Saharan Africa have received IPT. Many historical roadblocks to IPT scale-up are being addressed, but critical barriers remain, including the long duration of therapy (6-9 months), high pill burden (180-270 doses) and concerns about toxicity. In most settings, less than half of PLHIV initiating IPT complete the full course. A new 12-dose, once-weekly regimen of isoniazid and rifapentine (3HP) was recently shown to have similar efficacy, higher completion rates, and a better safety profile relative to nine months of IPT. But to achieve utilization and impact, it is essential to implement 3HP in a fashion that works for PLHIV in sub-Saharan Africa. The overall objective of this proposal is to identify a patient-centered delivery strategy that will facilitate 3HP uptake by PLHIV in sub-Saharan Africa. 3HP can either be directly observed by a healthcare worker (DOT) or self-administered (SAT); both options have relative advantages and disadvantages. We therefore propose to focus on shared decision-making as a method to optimize 3HP acceptance and completion. Our central hypothesis is that offering PLHIV an informed choice between theory-informed DOT and SAT strategies optimized to overcome key barriers to adherence will result in greater 3HP initiation and completion. In Aim 1, we will test our hypothesis by conducting a randomized trial among 1656 PLHIV in Kampala, Uganda, to compare acceptance and completion of 3HP using the following delivery strategies:
 1) Facilitated DOT; 2) Facilitated SAT; and 3) Patient choice (using a decision aid) between facilitated DOT and facilitated SAT. These interventions were specifically designed to overcome patient-level barriers to adherence using a new theoretical model of behavior change (COM-B). Facilitation of both DOT and SAT will include standardized counseling, streamlined clinic visits, reimbursement of visit-related costs, and SMS-based communication. Secondary outcomes include adverse events and TB incidence over one year following 3HP treatment.
 In Aim 2, we will employ a mixed methods approach to assess the implementation of core components of each delivery strategy, and whether or not they modified targeted barriers. 
Last, in Aim 3, we will perform empiric costing of each strategy and construct economic models to compare the costs and cost-effectiveness of the 3HP delivery strategies relative to each other, no preventive therapy and IPT. 3HP – the most promising intervention for TB prevention – will not be scaled up unless it can be delivered effectively and in a patient-centered fashion. Our proposed study employs an innovative approach of shared decision-making with a novel regimen to deliver a life-saving intervention (TB preventive therapy) that has been poorly adopted to date. 
This trial will address NIH and global priorities by providing the comprehensive evaluation needed to inform policy regarding 3HP scale-up among PLHIV in high TB-burden African settings.