Large-scale clinical trials conducted in Uganda and South Africa have shown that a novel pre-exposure prophylaxis (PrEP) medication, administered twice a year, completely protects young women from HIV infection. The research compared the efficacy of daily pills and an injection of lenacapavir in preventing HIV infection. PrEP refers to all three treatments. Principal investigator Linda-Gail Bekker, a physician-scientist, explains to Nadine Dreyer why this breakthrough is significant and what lies ahead for the South African portion of the study.
Trial Overview and Objectives
Lenacapavir and two other medications were tested for efficacy at three locations in Uganda and 25 sites in South Africa as part of the Purpose 1 trial, which enrolled 5,000 people. Lenacapavir, also known as Len LA, is a fusion capsid inhibitor that interferes with the HIV capsid, a protein envelope that protects HIV’s genetic material and replication-critical enzymes. It is administered subcutaneously every six months. The randomized controlled trial, funded by Gilead Sciences, tested several hypotheses.
The first hypothesis examined whether a six-monthly injection of lenacapavir was safe and offered better protection against HIV infection as PrEP for women aged 16 to 25 years than Truvada (F/TDF), a daily PrEP pill that has been widely used for over a decade.
The second hypothesis tested whether Descovy (F/TAF), a newer daily pill, was as effective as F/TDF. F/TAF has superior pharmacokinetic properties to F/TDF, meaning it moves through the body more effectively. F/TAF, a smaller pill, is currently used among men and transgender women in high-income countries.
The trial had three arms, with young women randomized in a 2:2:1 ratio (Len LA: F/TAF oral: F/TDF oral) in a double-blind manner. Neither the participants nor the researchers knew which treatment each person received until the trial concluded. Young women are the most commonly infected group with HIV in eastern and southern Africa, and many find it challenging to stick to a daily PrEP regimen for various structural and social reasons.
Trial Results
During the randomized phase of the trial, none of the 2,134 women who received lenacapavir contracted HIV, showing 100% efficacy. In comparison, 16 of the 1,068 women (1.5%) who took Truvada (F/TDF) and 39 of the 2,136 (1.8%) who received Descovy (F/TAF) contracted HIV. Following a recent independent data safety monitoring board review, it was recommended that the trial’s “blinded” phase be stopped, and all participants be offered a choice of PrEP.
The independent data safety monitoring board, an expert committee established at the start of the trial, reviewed unblinded data at specified times to monitor progress and safety, ensuring the trial did not continue if harm or a clear benefit in one arm was observed.
PrEP as Part of Comprehensive Prevention
PrEP should be made available alongside other prevention tools, such as HIV self-testing, condom access, STD screening and treatment, and contraception access for women who may become pregnant. Surgical male circumcision should also be an option for young men for health-related reasons. However, these measures alone cannot completely prevent new infections, particularly among youth.
For young people, the daily decision to use a condom or take a pill at the time of sexual intercourse can be challenging. HIV scientists and activists hope that making this “prevention decision” only twice a year will reduce unpredictability and barriers. For young women who struggle to attend clinic appointments or keep pills without facing stigma or violence, a biannual injection could be the key to staying HIV-free.
Future Steps for Drug Rollout
According to a Gilead Sciences press statement, the company will submit the dossier with all results to several country regulators, particularly in Uganda and South Africa, within the next couple of months. The World Health Organization will also review the data and may issue recommendations. Gilead has indicated that it will offer licenses to companies that produce generic drugs, a crucial step in reducing prices. Ideally, governments will be able to purchase the drug affordably and offer it to everyone who wants and needs protection against HIV.
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