POA · Pragmatic use of long-acting Oral Antiretrovirals in Africa

Despite tremendous/significant efforts to expand access to antiretroviral therapy (ART), in 2023 there were still 1.3 million new HIV infections worldwide and 630,00 HIV/AIDS-related deaths. There are 39.9 million people living with HIV worldwide (PLWH), and viral suppression rates for those on ART are below the UNAIDS target of 95%. Current ART guidelines recommend lifelong daily oral therapy which can be burdensome, and incomplete adherence risks treatment failure. Injectable long-acting (LA) ART formulations reduce the burden of taking tablets daily and could simplify adherence but are associated with implementation challenges in many settings. A novel regimen of weekly oral lenacapavir and Islatravir (LEN + ISL LA) has successfully completed phase II studies in the United States and could offer an LA treatment solution which is easier, both for individual patients and programmatic roll-out. However, no LEN + ISL LA trials have been conducted in sub-Saharan Africa, where 75% of PLWH live. We will conduct a phase III parallel-group, open-label, multi-country, multi-centre multi-country randomised, controlled trial in Uganda, Kenya, Côte d'Ivoire, and Zimbabwe. PLWH who are aged ≥18 years and virologically suppressed on daily oral first line ART (tenofovir, lamivudine, and dolutegravir) will be randomised to switch to LEN + ISL LA or remain on standard of care treatment. The primary outcome will be comparison of ongoing viral suppression rates between study arms at 48 weeks. We we will also use mixed Implementation Science methods to explore strategies, barriers, and facilitators for broader roll-out of oral LA ART, describe the overall pharmacokinetic profile of our new drugs across our study countries including some subpopulations, validate a urine assay for monitoring adherence, and carry out health economics evaluations to inform health policies. The project will be implemented by co-leads on each work packages to allow for capacity development.