Lenacapavir, a novel capsid inhibitor with a unique mechanism of action, has emerged as a highly effective pre-exposure prophylaxis (PrEP) for HIV, offering the convenience of twice-yearly injections. Clinical trial data presented at the World AIDS Conference in July 2024 sparked excitement, but the drug's high cost is a significant barrier to widespread use, particularly in regions with the greatest need.
Efficacy and Convenience
Lenacapavir's efficacy was demonstrated in the PURPOSE 1 trial (NCT04994509), a study conducted in South Africa and Uganda involving HIV-negative, sexually active cisgender women. Participants were randomized to receive lenacapavir every 26 weeks plus an oral placebo, daily oral emtricitabine with tenofovir alafenamide (F/TAF) with an injected placebo, or daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF) with an injected placebo. The results, published in the New England Journal of Medicine, showed that lenacapavir was 100% effective in preventing new HIV infections among the 2134 participants who received it. The incidence rate in the lenacapavir group was 0 per 100 person-years (95% CI, 0.00-0.19), compared to 2.02 per 100 person-years (95% CI, 1.44-2.76) for F/TAF and 1.69 per 100 person-years (95% CI, 0.96-2.74) for F/TDF.
Clara Lehmann, head of the German Center for Infection Research (DZIF) at the University Hospital of Cologne, described the atmosphere at the presentation of the data as "electrifying," highlighting the excitement surrounding the potential of lenacapavir.
One of the key advantages of lenacapavir is its infrequent dosing schedule. Unlike daily oral PrEP medications or even cabotegravir (CAB), which requires injections every one to two months, lenacapavir only needs to be administered twice a year. This can improve adherence, reduce stigma, and simplify treatment, especially for individuals in communities where HIV and PrEP are stigmatized or where daily medication adherence is challenging.
Cost and Accessibility
Despite its promise, the high cost of lenacapavir poses a significant challenge to its widespread adoption. Gilead, the manufacturer, charges more than €37,870 (approximately $40,000) per person per year for treatment. This is significantly higher than the cost of other PrEP medications, which average around €50-60 per month (€600-700 per year).
Gilead argues that the high price is necessary to recoup development costs. However, experts and AIDS activists contend that lenacapavir could be produced and sold at a much lower price. Andrew Hill, a British pharmacologist at the University of Liverpool, has estimated that lenacapavir could be sold for as little as $40 per year with a 30% profit margin.
To address the issue of affordability, Gilead is negotiating licenses with several generic drug manufacturers to produce and sell lenacapavir more cheaply in low-income countries. These licenses could include 120 countries, including some in sub-Saharan Africa. However, some countries, such as Argentina, Brazil, Mexico, and Peru, may not be included in this special licensing area, raising ethical and legal concerns.
Christine Stegling, the deputy director of UNAIDS, emphasized that "groundbreaking innovations will only lead us to a real decline in new infections if we ensure that all people have access to them."
The Ongoing Fight Against HIV
While new HIV infections have declined globally by 22% between 2010 and 2021, progress has stalled in recent years. According to the 2024 UNAIDS report, there were approximately 1.3 million new infections in 2023, and infection rates continue to rise in Central and Eastern Europe, Central Asia, North Africa, and the Middle East. Health experts aim to end the HIV epidemic by 2030, but achieving this goal will require a significant reduction in new infections.
Astrid Berner-Rodoreda, a post-doc researcher at the Heidelberg Institute of Global Health, noted that "if we really want to end the AIDS epidemic by 2030, then we would have to reduce the number of new infections to 370,000 next year."
Lenacapavir represents a significant advancement in HIV prevention, but its impact will depend on its accessibility and affordability. Overcoming the cost barrier will be crucial to ensuring that this promising new tool reaches the people who need it most.
