The possibility of eliminating the HIV epidemic has been a question lingering since the virus first appeared in the 1980s. Despite remarkable advancements, the world is still struggling with 1.3 million new infections annually. The ambitious United Nations goal of ending HIV/AIDS by 2030 feels out of reach. However, 2024 brought a spark of hope with a groundbreaking medical advancement: the drug lenacapavir.
Results from clinical trials have painted an optimistic picture for the future of HIV prevention. Lenacapavir has shown near-perfect effectiveness in stopping new infections, particularly through sexual transmission. This revolutionary development earned the title of Breakthrough of the Year by the journal Science, a recognition that underscores its potential to change the course of the HIV epidemic.
Lenacapavir’s development stems from years of meticulous research into the HIV capsid protein, a vital structure that protects the virus’s genetic material. The drug targets and stabilizes this protein, effectively blocking key stages of viral replication and transmission.
Two pivotal trials, PURPOSE 1 and PURPOSE 2, have demonstrated lenacapavir’s extraordinary efficacy. PURPOSE 2, a study sponsored by Gilead Sciences, involved over 3,200 participants, including cisgender men, transgender men, transgender women, and gender non-binary individuals who have sex with partners assigned male at birth. Conducted across diverse locations such as Argentina, Brazil, South Africa, and Thailand, the trial revealed an astonishing 96% effectiveness in preventing HIV infections.
Equally compelling were the findings from PURPOSE 1, which focused on 5,300 cisgender women in South Africa and Uganda. In data shared at the AIDS 2024 conference in Munich, the trial reported 100% efficacy. Not a single woman who received the drug since the study began in 2021 contracted HIV, showcasing the drug’s unmatched preventive potential.
Ethel Weld, an assistant professor of medicine at Johns Hopkins University, hailed the results as a “thrilling game changer for HIV prevention.” The drug’s impact, she explained, lies in its ability to reduce the burden of daily medication and empower individuals with a more manageable prevention option.
Lenacapavir is administered via a twice-yearly injection, offering a much-needed alternative to the current daily pill regimen for pre-exposure prophylaxis (PrEP). While oral PrEP drugs like Truvada have been shown to be 99% effective in clinical trials, real-world adherence to daily medication has been a persistent challenge.
Many individuals struggle with stigma, inconvenience, or misconceptions surrounding oral PrEP. For example, women in South Africa have reported fearing judgment from partners who might assume they already have HIV or are sexually promiscuous. Among men who have sex with men, factors like access to medication and perceived necessity further hinder adherence. Studies have found that oral PrEP’s real-world effectiveness can drop as low as 26% in certain populations, especially younger men.
The PURPOSE trials highlighted these challenges, as participants randomized to receive oral PrEP displayed significantly lower adherence compared to those who received lenacapavir injections. This underscores the transformative potential of lenacapavir’s biannual dosing schedule, which Weld likens to preventive paradigms like vaccination.
Advocacy groups have also embraced lenacapavir with enthusiasm. The People’s Medicines Alliance, a global coalition of over 100 organizations spanning 33 countries, called the drug a “real game-changer,” particularly for marginalized populations in low- and middle-income countries.
Cécile Tremblay, an HIV researcher at the University of Montréal, emphasized lenacapavir’s potential to tackle the epidemic in sub-Saharan Africa, a region bearing the highest disease burden. Despite representing only 10% of the global population, sub-Saharan Africa accounts for two-thirds of people living with HIV—25.7 million out of 38.4 million worldwide. Every week, an estimated 4,000 teenage girls and young women in the region contract HIV.
Tremblay noted that lenacapavir’s high efficacy is especially remarkable given the challenges faced by oral PrEP in this population, where stigma and discrimination often prevent consistent use.
Although lenacapavir has been FDA-approved since 2022 for treating multi-drug-resistant HIV, its use in prevention is a new frontier. Gilead Sciences plans to submit regulatory filings for approval of lenacapavir as a preventive treatment by the end of 2024, aiming for a global market launch in 2025.
Challenges remain, particularly regarding cost and accessibility. Lenacapavir’s price for HIV treatment in the United States was $42,250 per year in 2023, a stark contrast to oral PrEP options, which can cost less than $4 a month. For widespread adoption in regions like South Africa, analysts estimate that annual costs would need to drop below $54 per patient.
Advocates stress the importance of building infrastructure to ensure at-risk populations can access this life-saving drug. Tremblay believes that if lenacapavir becomes widely available, it could significantly reduce HIV transmission rates and ultimately bring the epidemic to a halt.
Linda-Gail Bekker, director of the Desmond Tutu HIV Centre at the University of Cape Town, echoed this sentiment. She emphasized the urgency of ensuring that communities involved in the lenacapavir trials, particularly in low-income regions, gain access to the drug, whether through its original manufacturer or future generic options.
Lenacapavir’s journey represents a beacon of hope in the fight against HIV/AIDS. If its promise is realized, this groundbreaking drug could transform lives and move the world closer to ending the HIV epidemic once and for all.