HIV is still a serious health problem in many parts of Africa, especially for teenage girls and young women. In Kenya, more than 1.4 million people are living with HIV. Girls and young women between the ages of 16 and 30 are more likely to get infected with HIV than others, mainly because of things like limited access to protection, social pressure, and unequal relationships. Although there are medicines that can help prevent HIV, like the daily PrEP pill, many people find it hard to take a pill every day. A long-acting, PrEP option given as an injection called Cabotegravir, every 2 months, was approved by the United States of America Food and Drug Administration (US FDA) in 2021 and added to WHO recommendations in July 2022. Cabotegravir for PrEP is currently approved in many countries worldwide. While cabotegravir was shown to prevent HIV-1 more than daily oral PrEP in clinical studies, it is not readily available in many countries. To help with this, a company called Merck Sharp & Dohme (MSD) has developed a new HIV prevention pill called MK-8527, which only needs to be taken once a month. This study is being done to find out if MK-8527 is safe and works well in preventing HIV, compared to the daily PrEP pill called FTC/TDF (Truvada), which is currently in use.

The study, named MK-8527-010-00, is being done in Kenya, Uganda, and South Africa. It includes women between the ages of 16 and 30 who are more likely to get infected with HIV, especially those with multiple partners, not using condoms regularly, or having had a sexually transmitted infection. The women in the study will be placed into two groups by chance: one will take the new monthly pill (MK-8527), and the other will take the regular daily PrEP pill. Neither the participants nor the doctors will know which pill each person is taking until the study is over — this is called a double-blind study to make the results more accurate. Across all countries, about 4,580 women will join the study. In Kenya, the Rachuonyo Clinical Research Site, located at Rachuonyo South County Hospital in Homa Bay County, will enroll at least 200 women. Participants will visit the clinic once a month for up to two years to receive their medication, get tested for HIV, and have their health checked.

If a participant becomes pregnant during the study, she can choose to continue in the study with the currently approved medication (daily PrEP) after discussing the benefits and risks with the study team. With her permission, her baby may also be checked and followed for up to a year to make sure everything is okay.

The study will also check how easy it is for participants to take the pill, how they feel about it, and how the drug works in their body. If anyone gets HIV during the study, more tests will be done to understand how and why that happened.

The results of this study could offer a new, easier-to-use option for HIV prevention, especially for young women who have trouble taking a pill every day. If the monthly pill works well, it could help reduce new HIV infections in Kenya and in other parts of the world.

The burden of HIV-1 infection remains disproportionately high among adolescent girls and young women in sub-Saharan Africa, including Kenya. While daily oral pre-exposure prophylaxis (PrEP) has demonstrated effectiveness in preventing HIV acquisition, adherence to daily dosing remains a significant barrier to optimal use. MK-8527 is a novel nucleoside reverse transcriptase translocation inhibitor (NRTTI) developed by Merck Sharp & Dohme (MSD) for once-monthly oral PrEP. Due to its high potency and long half-life, MK-8527 has the potential to reduce the risk of HIV acquisition without relying on adherence to a daily regimen

This study is a Phase III randomized, double-blind, active-controlled, multicentre clinical trial (protocol MK-8527-010-00) designed to assess the efficacy, safety, and tolerability of MK-8527 administered once monthly compared to the standard daily oral FTC/TDF regimen. The primary objective of this study is to evaluate the efficacy, safety, and tolerability of MK-8527 monthly compared to FTC/TDF daily for the prevention of HIV-1 infection as assessed by the incidence rate per year of adjudicated HIV-1 infections and the number of adverse events reported leading to discontinuation of study intervention. The study will enrol approximately 4,580 HIV-negative cisgender women (assigned female at birth and who identify as women) aged 16 to 30 years who are at increased risk of HIV-1 acquisition, defined as those with behavioral, biological, or partner-based risk factors (e.g., history of STIs, condomless sex with multiple or HIV-positive partners). Participants will be randomized in a 1:1 ratio to receive either MK-8527 (11 mg monthly) or FTC/TDF (200 mg/245 mg daily), with matched placebo to preserve blinding. Study interventions will be administered for up to 24 months, followed by a 28-day open-label follow-up period.

At the Rachuonyo Clinical Research Site located within Rachuonyo South County Hospital in Homa Bay County, Kenya, at least 200 participants will be enrolled. The site was selected due to its experienced research infrastructure, high HIV burden in the catchment population, and strong community engagement mechanisms. Participants will attend monthly visits for HIV testing, medication dispensation, adherence assessments, safety evaluations, and pharmacokinetic sampling. Participants who become pregnant may continue in the study on open-label daily FTC/TDF, with optional infant follow-up to 1 year of age to assess safety, growth, and potential HIV transmission.