July 2024, we received the long-awaited results from the first of 2 studies evaluating twice-yearly injectable lenacapavir for preexposure prophylaxis (PrEP) against HIV infection. PURPOSE 1(NCT04994509), conducted in South Africa and Uganda, enrolled HIV-negative, sexually active cisgender women. Participants were randomly assigned 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. Rather than including a placebo group, the study investigators compared each group’s efficacy against the background rate of HIV infection observed during screening.1
The study’s results were highly promising: lenacapavir was 100% effective in preventing new HIV infections among the 2134 participants who received it. The study’s design also provided additional insights. Among the 8094 screened participants, the background HIV incidence was 2.41 per 100 person-years (95% CI, 1.82-3.19). In the lenacapavir group, the incidence was 0 per 100 person-years (95% CI, 0.00-0.19); for F/TAF, it was 2.02 per 100 person-years (95% CI, 1.44-2.76); and for F/TDF, it was 1.69 per 100 person-years (95% CI, 0.96-2.74).1 Not only did lenacapavir outperform the oral regimens (0 is difficult to surpass), but the rates for the oral regimens were not significantly different from the background HIV infection rate. The low adherence rates to the oral regimens were notable, with breakthrough infections largely occurring in patients who had low or undetectable concentrations of tenofovir.
The potential benefits of effective, twice-yearly injectable therapy are immense. Although PrEP has shown promise since the early success of F/ TDF, its major limitation has been adherence. Daily oral medications, though common for many people, require a committed and educated patient population, particularly when taken by healthy individuals not taking other medications. This challenge is exacerbated in populations where stigma surrounding HIV and PrEP is strong. Injectable medications such as lenacapavir could bypass this issue by offering a more private method of administration. Furthermore, a medication that only needs to be administered infrequently enhances privacy and simplifies treatment.
As this groundbreaking therapy nears availability, practical questions arise. The most pressing relate to cost. How can a therapy that costs thousands of dollars per year in the US be made accessible to individuals in high-need countries who cannot afford a fraction of that price? There is some time to address these concerns. Gilead Sciences is awaiting the results of PURPOSE 2 (NCT04925752) in late 2024 or early 2025 before filing for PrEP approval. The company has made promising statements, including that the new price will not be based on its current price for treatment-experienced patients, that they will pursue voluntary licensing partners in other countries, and that they will ensure a dedicated supply of medication until those partners are ready.2
We will have to see how well these commitments translate into action. Disparities in access to health care resources continue to fuel the spread of HIV, and the availability of new therapies can exacerbate inequities. Gilead has a historic opportunity to be a significant part of the solution.
