R01AI155052

Co-Benefits of Co-Delivery of Long-Acting Antiretrovirals and Contraceptives - Project Summary

The first complete long-acting (LA) formulation of an antiretroviral therapy (ART), injectable cabotegravir and rilpivirine, is at the cusp of clinical approval. This is a potential game-changing development in the HIV treatment field. LA ART regimens increase options for patients and providers to improve patient adherence and persistence to treatment.

Several subpopulations, including adolescent girls and young women (AGYW, ages 15-24), lag behind the 3rd 90-90-90 UNAIDS goal of viral suppression, including in Kenya. AGYW living with HIV (AGYWLHIV) face unique challenges in persistence to ART, and LA ART options have the potential to help overcome some of these challenges through greater confidentiality and reduced stigma compared to oral ART.

Another major threat to AGYW's health is unintended pregnancies, and AGYWLHIV also face unique challenges in uptake and continuation rates of LA contraceptives. More recently, the use of LA contraceptives, which include injectable and implantable methods, has gained marked momentum in Kenya, where many HIV treatment programs have integrated contraceptive provision into routine HIV care, including for AGYW. Furthermore, AGYWLHIV are highly interested in co-delivery of ART and contraceptives. However, co-delivery also raises potential issues, both pharmacological and behavioral, that require further investigation.

We propose foundational pharmacokinetic (PK) and qualitative studies leading up to a hybrid type I effectiveness-implementation trial randomizing individual AGYWLHIV to receive LA injectable cabotegravir/rilpivirine vs. standard of care in Kenya. Our central premise is that the use of LA ART will foster long-term thinking for health, including for pregnancy prevention, and that leveraging existing LA contraceptive delivery platforms will make LA ART highly feasible.

Aim 1A will determine if combined injectable cabotegravir/rilpivirine use has any bidirectional drug-drug interactions with injectable or implantable contraceptives. The method will involve a parallel group PK evaluation with repeat plasma sampling among cabotegravir/rilpivirine users initiating injectable or implantable contraceptives vs. those not using any hormonal contraceptives (total 5 groups, N=21 per group).

Aim 1B will qualitatively explore points of convergence and divergence, preferences and values, and health systems readiness around wider-scale co-delivery of LA ART/contraceptives. The method will involve 20-40 serial, semi-structured, in-depth interviews with AGYW from the above sentinel cohort, and 2-4 focus group discussions with providers, policymakers, and stakeholders.

Aim 2 will evaluate the impact of co-delivery of LA ART and contraceptives among AGYWLHIV via a hybrid trial on: (A) effectiveness outcomes of HIV treatment (viral suppression [primary outcome] and adherence/persistence) and contraception (uptake and continuation rates), and (B) implementation outcomes of acceptability, feasibility, and fidelity. The method will involve an open-label, clinic-provided, mixed methods hybrid trial, randomizing AGYW 1:1 to switch to injectable cabotegravir/rilpivirine (intervention arm) vs. to continue their current oral ART regimen (control arm; total N=550).

University Of Alabama At Birmingham

NOT APPLICABLE

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Birmingham, Alabama 352940004 United States

Single Zip Code

Research Project Grant (Parent R01 Clinical Trial Required) (PA-20-183)

Amendment Since initial award the End Date has been extended from 03/31/26 to 03/31/27 and the total obligations have increased 333% from $715,797 to $3,102,332.