A large clinical trial conducted in South Africa and Uganda has revealed that a twice-yearly injection of lenacapavir provides complete protection against HIV infection in young women. The Purpose 1 trial, involving 5,000 participants, compared the six-month injection of lenacapavir to two daily oral pre-exposure prophylaxis (PrEP) drugs, Truvada (F/TDF) and Descovy (F/TAF). The study's findings offer a promising new approach to HIV prevention, particularly for populations where adherence to daily medication regimens is challenging.
The trial, sponsored by Gilead Sciences, randomly assigned young women aged 16-25 to one of three arms: lenacapavir injection every six months, daily oral Descovy (F/TAF), or daily oral Truvada (F/TDF) in a 2:2:1 ratio. The primary endpoint was HIV infection rate within each arm. The results showed that none of the 2,134 women who received lenacapavir contracted HIV, demonstrating 100% efficacy. In contrast, 16 of the 1,068 women (1.5%) who took Truvada and 39 of 2,136 (1.8%) who received Descovy contracted HIV.
Significance of the Findings
The results are particularly significant because young women in eastern and southern Africa are disproportionately affected by new HIV infections and often face challenges adhering to daily PrEP regimens. According to UNAIDS, there were 1.3 million new HIV infections globally in the past year. While this is a decrease from the 2 million infections in 2010, it is insufficient to meet the 2025 target of fewer than 500,000 new infections or the goal of ending AIDS by 2030. Lenacapavir's twice-yearly administration could overcome adherence barriers and significantly reduce new infections in this vulnerable population.
Dr. Linda-Gail Bekker, principal investigator for the South African part of the study, emphasized the potential impact: "For a young woman who struggles to get to an appointment at a clinic in a town or who can’t keep pills without facing stigma or violence, an injection just twice a year is the option that could keep her free of HIV."
Next Steps
Following a review by an independent data safety monitoring board, the trial's blinded phase was halted, and all participants are now being offered a choice of PrEP. The trial will continue in an open-label phase, where participants are informed of their original treatment assignment and can choose their preferred PrEP method.
A sister trial, Purpose 2, is also underway, evaluating lenacapavir in cisgender men, transgender individuals, and nonbinary people who have sex with men. These trials are crucial to assess the drug's effectiveness across diverse populations and modes of HIV transmission.
Gilead Sciences plans to submit the trial data to regulatory authorities in Uganda and South Africa, as well as to the World Health Organization (WHO). Regulatory approval and WHO endorsement could pave the way for the drug's inclusion in national and international HIV prevention guidelines. Furthermore, Gilead intends to offer licenses to generic drug manufacturers to ensure affordability and accessibility in resource-limited settings.
Mechanism of Action
Lenacapavir is a fusion capsid inhibitor that interferes with the HIV capsid, a protein shell that protects the virus's genetic material and enzymes needed for replication. Administered subcutaneously, it offers a long-acting PrEP option with the potential to significantly impact the global HIV epidemic.
