HIV remains a major global health issue. In 2023, about 40 million people worldwide were living with HIV, and there were about 1.3 million new infections. The highest number of new HIV infections continues to occur among women and girls in Sub-Saharan Africa.To help prevent HIV, a type of medicine called PrEP (pre-exposure prophylaxis) is used. This is usually taken as a daily pill. However, taking a pill every day can be difficult for some people. There are also injectable prevention options, but they are not widely available and may not be preferred by everyone.

This research study is testing an experimental drug called MK-8527, a once-monthly pill designed to prevent HIV infection. A monthly pill may be more appealing to young women who struggle with taking daily medication, dislike injections, or have limited access to injectable PrEP. The study will enroll female participants between the ages of 16 and 30 who do not have HIV and may benefit from HIV prevention medication. The study will be conducted at several research sites across three African countries, South Africa, Uganda, and Kenya. There are 4 sites in Kenya.

The aim is to find out how well the monthly MK-8527 pill works to prevent HIV infection and how safe it is compared to the standard daily PrEP pill, FTC/TDF.

Participants will be randomly assigned to one of two groups: one group will take the monthly MK-8527 pill, and the other will take the standard daily PrEP pill (FTC/TDF). To make sure the study is fair and unbiased, everyone will also take another pill that looks like the other group’s medicine but does not contain the actual drug. This allows researchers to compare the two treatments without anyone knowing which pill they are receiving.

Participants will visit the study site once a month for about 24 months. During these visits, they will have HIV and pregnancy tests, health check-ups, and other assessments to monitor how well the medicine is working. There will also be a short follow-up period after the treatment period ends. If a participant becomes pregnant and chooses to continue in the study, she will have additional health checks, including blood tests.

If the study is successful, MK-8527 could offer a simpler and more acceptable way for women to protect themselves against HIV especially in areas with high HIV prevalence and taking a pill every day is challenging.

Background: 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) with potent antiretroviral activity against HIV-1, being developed for the prevention of HIV-1 infection because of its potent antiviral activity, long half-life, and favourable safety profile as demonstrated in early-phase clinical studies. Nonclinical and clinical data indicate that MK-8527 is generally well tolerated. The convenience and discretion of monthly oral administration of MK-8527 may facilitate adherence and access to PrEP for women at high risk for HIV-1 infection, ultimately leading to greater effectiveness for HIV-1 prevention than what is currently observed with daily oral emtricitabine/tenofovir disoproxil (FTC/TDF).

Objectives: 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 and any adverse event leading to discontinuation of study intervention.

Methods: This is a randomized, active-controlled, parallel-group, multisite, double-blind, double-dummy study to evaluate the efficacy and safety of monthly oral MK-8527 in cisgender women 16 to 30 years of age, who are at a greater likelihood of HIV-1 exposure. The active comparator for this study will be oral daily FTC/TDF. Approximately 4580 participants from Africa will be randomized and stratified by age in a 1:1 ratio to receive either MK-8527 or FTC/TDF for the duration of the study. Approximately 80% of participants will be ≤25 years of age. KEMRI-CCR PHRD Thika site will enrol approximately 150 participants. Participants will be assessed every month till month 24, with an additional follow-up at day 28 and day 42 post-end of treatment.

Expected outcome: The primary hypothesis is that oral monthly MK-8527 is superior to oral daily FTC/TDF with respect to the hazard ratio for HIV-1 infection and the number of adverse events reported leading to discontinuation of the study intervention.