Layman’s Summary

Adolescent girls and young women (AGYW) lag behind older women in viral suppression. Long-acting antiretroviral therapy (LA ART) can increase options, patient adherence and persistence to treatment. In resource-limited settings (RLS), LA ART regimens may also ease the burden on health systems by decreasing refill visits or easing supply chain management. Unintended pregnancies greatly affect AGYW. Long-acting contraceptives (e.g., LARCs and injectables) can prevent unintended pregnancies. RLS have decades of investments in contraceptive delivery. LA ART can leverage LA contraceptive delivery platforms. We speculate that using L ART will increase the demand for LAC among AGYW, using LARCs will increase the demand for L ART among AGYW (advantages will be on both sides), that taking advantage of the LARCs platforms to provide the LART to AGYW will be highly acceptable, feasible, and deliverable to all stakeholders (e.g. the AGYW, the healthcare workers, the management and policy makers).

Study objectives:

1 (a): To find out more about how the body responds to L AART (Pharmacokinetic (PK) study). This will include assessing the blood levels of the LAART, as well as the blood level of the LARCs and seeing if the two are affecting each other’s blood levels. Low blood levels of any drug in the body that is needed may reduce the effectiveness of the drug. High blood levels that is needed may increase the unexpected medical problems of the drug. Other studies have found that these two are safe when used together, as well as effective. We intend to do this so that AGYW can benefit from both drugs 1 (b): To find out what stakeholders think about the L ART (Qualitative study). This will include what stakeholders think are the strengths and challenges of providing LART to AGWY. For LART to be included for routine use, all stakeholders need to be on board. We hope to provide information for policy makers to use when planning to roll out LART for routine use by AGYW 2 (a): To compare the outcomes of using LART compared to those HIV negative but on contraceptives (comparing the contraceptive drug levels in blood) and those HIV positive but not on hormonal contraceptive (comparing HIV outcomes such as drug adherence, viral loads etc. This is the Hybrid type I effectiveness-implementation trial. 2 (b): To evaluate the impact providing L ART to AGYW: We will assess, after implementing the study, how acceptable and feasible it is providing both drugs. Study site: The proposed study will be conducted in HIV treatment facilities in western Kenya within the regional Moi Teaching and Referral Hospital (MTRH).

Background: Several subpopulations, including adolescent girls and young women (AGYW, ages 15-24), lag behind the 3rd 90-90-90 UNAIDS goal of viral suppression, particularly in resource-limited settings (RLS).1 AGYW living with HIV (AGYWLHIV) face unique challenges in persistence to anti-retroviral therapy,2 and overcoming barriers such as stigma and poverty that hinder achieving viral suppression among AGYW.5 Long-acting (LA) antiretroviral therapy (ART), such as injectable cabotegravir and rilpivirine, has been receiving global clinical approvals and has the potential to address these barriers 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,3 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.

Methods: 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 from the PARVI study (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).

Impact: 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. This study also directly addresses the need to find interventions that will and achieve the UNAIDS 90-90-90 goals.