A groundbreaking clinical trial in South Africa and Uganda has demonstrated that a new pre-exposure prophylaxis (PrEP) drug, administered via a twice-yearly injection, provides total protection against HIV infection in young women. The trial, involving 5,000 participants, tested the efficacy of lenacapavir, a fusion capsid inhibitor, against two other daily PrEP pills, Truvada (F/TDF) and Descovy (F/TAF).
The Purpose 1 trial, led by physician-scientist Linda-Gail Bekker, aimed to evaluate whether lenacapavir's six-month injection could offer superior protection against HIV compared to the established daily pills. Lenacapavir works by interfering with the HIV capsid, a protein shell essential for the virus's replication. This method, requiring only biannual administration, represents a significant advancement for women aged 16-25, who often struggle with maintaining a daily medication regimen due to various social and structural challenges.
The trial was a randomized, controlled study sponsored by Gilead Sciences. Participants were divided into three groups: those receiving lenacapavir injections, those taking Truvada, and those on Descovy. The trial was double-blinded, ensuring neither participants nor researchers knew which treatment was being administered until the study's conclusion.
Results revealed that none of the 2,134 women who received lenacapavir contracted HIV, demonstrating 100% efficacy. In contrast, 16 of the 1,068 women on Truvada and 39 of the 2,136 women on Descovy contracted HIV, highlighting the superior protection offered by lenacapavir.
An independent data safety monitoring board reviewed these results and recommended ending the trial's blinded phase. All participants will now be offered their choice of PrEP. This decision underscores the trial's success and the potential of lenacapavir as a highly effective HIV prevention tool.
The significance of this breakthrough cannot be overstated. With 1.3 million new HIV infections globally last year, innovative prevention methods are crucial. While current strategies, including PrEP, HIV self-testing, condom use, and STI screening, have reduced infection rates, they have not eradicated new infections, particularly among young people. The convenience of a biannual injection may address the adherence challenges faced by young women, offering a more practical and stigma-free prevention option.
Looking ahead, the Purpose 1 trial will continue in an open-label phase, where participants will be informed of their treatment group and can choose their preferred PrEP method. Meanwhile, a sister trial, Purpose 2, is underway, targeting cisgender men, transgender, and nonbinary individuals who have sex with men, to ensure the drug's efficacy across diverse populations.
Gilead Sciences plans to submit the trial results to regulatory authorities in Uganda and South Africa, as well as the World Health Organization, which may issue recommendations based on the findings. The goal is to incorporate lenacapavir into WHO and national guidelines and make it accessible to those in need through affordable pricing and generic drug manufacturing.
Linda-Gail Bekker, a professor of medicine and deputy director of the Desmond Tutu HIV Centre at the University of Cape Town, expressed optimism that this new drug could become a critical tool in the fight against HIV, offering hope for a future free of new infections.
