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HIV Infections Clinical Trial

Official title: Co-benefits of Co-delivery of Long-acting Antiretrovirals and Contraceptives

Status Recruiting

Clinical Trial Summary

The study investigators are conducting foundational pharmacokinetic (PK) and qualitative studies, among 15-24 years old (inclusive) adolescent girls and young women living with HIV (AGYWLHIV) already on oral antiretroviral therapy (ART) and virally suppressed, leading up to a hybrid type I effectiveness-implementation trial randomizing individual AGYWLHIV to receive long-acting (LA) injectable cabotegravir/rilpivirine vs. standard of care within one of Kenya's largest HIV treatment programs. The PK and qualitative studies will investigate potential issues arising from co-delivery and guide delivery of the effectiveness-implementation trial. The PK and qualitative studies will largely be conducted with a sentinel cohort of AGYWLHIV. Learning from this early LA ART use, the investigators will refine the procedures in the LA ART hybrid trial.

Clinical Trial Description

Long-acting (LA) antiretroviral therapy (ART), such as injectable cabotegravir and rilpivirine, has been receiving global clinical approvals and has the potential to address barriers to ART and improve patient adherence and persistence to treatment. LA ART regimens can potentially also increase options for patients and providers to individualize treatment plans, provide a powerful treatment option for those experiencing adherence issues related oral treatment options, and may ease the burden of health systems in RLS. Another major threat to AGYW's health is unintended pregnancies and AGYWLHIV also face unique challenges in uptake and continuation of LA contraceptives. Use of LA ART may foster synergy in usage of LA contraceptives among AGYWLHIV. This proposed research study has three main components: 1) a prospective, non-randomized, parallel-group pharmacokinetic (PK) study among a sentinel cohort of five distinct groups of AGYW, and will leverage existing control groups (Aim 1a); 2) a qualitative study that will conduct individual interviews with four different subgroups of AGYWLHIV from the sentinel cohort from the PK study, as well as focus group discussions with providers, policy makers, and other stakeholders for health systems readiness for wider scale-up (Aim 1b); and 3) an open-label, mixed methods, 48-week type I hybrid trial randomizing AGYW with viral suppression on their current ART regimen to switch to 1:1 cabotegravir/ rilpivirine (intervention arm) vs. continue their oral ART regimen (Aim 2a), with a component also evaluating implementation outcomes of acceptability, feasibility, and fidelity (Aim 2b). The proposed study will be conducted in HIV treatment facilities in western Kenya within the regional Moi Teaching and Referral Hospital (MTRH). This study will provide foundational data for future studies and implementation plans related to addressing barriers and will critically inform follow-up studies of LA ART in other priority subpopulations. Providing an array of method options for both HIV treatment and pregnancy prevention has the potential to revolutionize personal decision-making and improve long-term outcomes for AGYWLHIV. Our real-world experiences of co-delivery will also inform future considerations for co-formulations of antiretrovirals and contraceptives for both HIV treatment and prevention. Our central hypothesis is the following: 1) at the client level, the use of LA ART or contraceptives will foster long-term thinking for health, forging a convergence of the use of the two when applicable; and 2) at the program/provider level, leveraging existing LA contraceptive delivery platform will make LA ART highly acceptable, feasible, and deliverable with high fidelity. Our overall objective in this study is to conduct the foundational PK and qualitative studies first as a lead in to the hybrid trial. Guided by Proctor et al.'s implementation outcomes framework, the hybrid trial will also focus on acceptability, feasibility, and fidelity. These implementation outcomes are proximal indicators of implementation processes and intermediate outcomes, which ultimately predict implementation success. Demonstrating successful implementation outcomes will then inform wider-scale implementation of LA ART, when service and client outcomes can be fully realized. The PK and qualitative studies will investigate potential issues arising from co-delivery and guide delivery of the effectiveness-implementation trial. The PK (Aim 1a) and qualitative (Aim 1b) studies will largely be conducted with a sentinel cohort of AGYWLHIV in parallel to each other. Learning from this early LA ART use, the investigators will refine our procedures in the LA ART hybrid trial (Aim 2). For all possible outcomes/scenarios of Aim 1, the investigators still anticipate conducting a robust trial in Aim 2. Thus, our specific aims are: Aim 1: To collect foundational data to better inform design of an effectiveness-implementation trial. Aim 1a: To determine if combined cabotegravir/rilpivirine injectable use has bidirectional drug-drug interactions with injectable (depot medroxyprogesterone acetate [DMPA]) or implantable (etonogestrel or levonorgestrel) contraceptives. Aim 1b: To qualitatively explore points of convergence and divergence, preferences and values, and health systems readiness around wider-scale co-delivery of LA ART and contraceptives. Aim 2: To evaluate the impact of clinic-provided, co-delivery of LA ART and contraceptives among AGYWLHIV. Aim 2a: To evaluate the impact on effectiveness outcomes of HIV treatment (viral suppression and adherence/persistence) and contraception (uptake and continuation rates). Aim 2b: To evaluate the impact on implementation outcomes of acceptability, feasibility, and fidelity. ;

Related Conditions & MeSH terms

• Contraception
• Drug-drug Interaction
• HIV Infections

• NCT number: NCT05044962
• Study type: Interventional
• Source: University of Alabama at Birmingham
• Contact: Rena Patel, MD, MPH
• Phone: 205.934.8145
• Email: renapatel@uabmc.edu
• Status: Recruiting
• Phase: N/A
• Start date: November 26, 2021
• Completion date: March 31, 2025