Editor's Note: On July 24th, during the highly anticipated Co-Chairs' Choice session at the 25th International AIDS Conference in Munich, Germany, the PURPOSE 1 study was unveiled, highlighting a significant breakthrough in HIV prevention. The study demonstrated the exceptional efficacy of the long-acting injectable drug Lenacapavir in preventing HIV infection among women. The study was simultaneously published online in The New England Journal of Medicine. Conducted in South Africa and Uganda, this double-blind, randomized controlled trial compared different prevention strategies and found that biannual injections of Lenacapavir effectively blocked HIV infection, resulting in zero cases of infection. The efficacy of Lenacapavir far surpassed that of daily oral F/TAF and F/TDF. The study not only confirmed Lenacapavir's high effectiveness but also revealed its potential to improve patient adherence, offering a new solution to one of the major challenges in HIV prevention. With the widespread application of Lenacapavir, global HIV prevention strategies may be poised for significant change. Infectious Diseases Frontier invited Dr. Hui Wang from the Second Affiliated Hospital of Southern University of Science and Technology (Shenzhen Third People's Hospital) to provide an in-depth commentary and analysis of this study.This study employed a double-blind, randomized, controlled trial design to evaluate the efficacy and safety of Lenacapavir as a pre-exposure prophylaxis (PrEP) strategy for HIV prevention in adolescent girls and young women in South Africa and Uganda. A total of 5,338 initially HIV-negative participants were randomly assigned to three treatment groups: Lenacapavir (subcutaneous injections once every 26 weeks), daily oral F/TAF, and daily oral F/TDF. The study observed 55 new HIV infections during the trial, with 0 infections in the Lenacapavir group, 39 in the F/TAF group, and 16 in the F/TDF group. Compared to the background HIV infection rate, the infection rate in the Lenacapavir group was significantly lower, demonstrating its outstanding efficacy in preventing HIV infection. Lenacapavir also significantly reduced the risk of HIV infection compared to daily oral F/TAF, providing a new and effective option for HIV prevention. The study found lower adherence rates in the F/TAF and F/TDF groups, highlighting the potential of Lenacapavir’s long-acting nature and higher adherence for individuals who struggle with daily medication adherence. This finding is significant for advancing global HIV prevention strategies.
Expert Commentary
Lenacapavir is an HIV capsid inhibitor that interferes with multiple critical stages of the HIV replication cycle by modulating the stability and/or transport of the capsid complex. It was first approved for marketing in Europe in August 2022, followed by FDA approval in December of the same year. It is currently the only HIV treatment drug globally approved for biannual administration. The PURPOSE 1 study aimed to validate the efficacy of twice-yearly injections of Lenacapavir in preventing HIV infection in women.
Lenacapavir is undoubtedly a milestone drug. On one hand, it is the first PrEP drug to achieve 100% effective HIV prevention in a Phase III clinical trial, outperforming TDF/FTC and TAF/FTC. It avoids the issue of declining adherence over time seen with oral drugs. At 52 weeks, 92.8% of participants in the Lenacapavir group received their injections on time, demonstrating that long-acting injectables can effectively improve adherence and reduce the risk of HIV infection due to poor adherence.
On the other hand, the PURPOSE 1 study included women aged 16 to 25, a group known to be at higher risk of HIV infection through sexual contact due to their physiological structure. There is an urgent need to strengthen prevention efforts in women in high-risk areas. The PURPOSE 1 study demonstrated the effectiveness of Lenacapavir in preventing HIV infection in women, with a safety profile in pregnancy outcomes similar to that of the oral drug control groups (F/TAF and F/TDF).
Overall, the twice-yearly injectable Lenacapavir is a safe and effective PrEP drug, with superior preventive efficacy compared to existing oral PrEP drugs. We will continue to monitor and look forward to the results of PURPOSE 2-5 trials in other populations.
