Lenacapavir, a Twice-Yearly Injectable Drug for HIV Prevention That Should be Widely Available
Health Letter, May 2025
By Robert Steinbrook, M.D.
Director, Public Citizen's Health Research Group
Pre-exposure prophylaxis (PrEP) is taken to reduce the risk of contracting human immunodeficiency virus (HIV) infection from sex or intravenous drug use. Before starting prophylaxis, people must have a negative HIV test, and their HIV-negative status must be confirmed during treatment. PrEP does not protect against other sexually transmitted infections.
In clinical trials sponsored by the drug’s manufacturer with thousands of participants, lenacapavir, a twice-yearly injectable drug, was highly effective in preventing HIV infection when taken as directed. If it were widely available at low cost, lenacapavir could help protect millions of people worldwide against HIV infection.
Lenacapavir is not an HIV vaccine. However, at present, this drug, which protects against HIV infection and is administered every six months, is as close to a HIV vaccine as we have. There are vaccines, such as the influenza vaccine (flu shot) and the COVID-19 vaccine for people who have previously been vaccinated, that are taken once a year. For high-risk individuals and people ages 65 and older, a booster shot of the COVID-19 vaccine is recommended every six months.
To prevent HIV infection, lenacapavir is highly effective, thermostable (meaning that it can be shipped and stored at room temperature), has not raised safety concerns, and is available now.
In one recent trial, known as PURPOSE 1, twice-yearly lenacapavir provided complete (100%) protection against HIV infection in women whose gender identity corresponded with their sex at birth. The second trial, known as PURPOSE 2, included men whose gender identity corresponded with their sex at birth and gender-diverse persons. In PURPOSE 2 the incidence of HIV infection was 89% lower with lenacapavir than for participants taking the standard PrEP regimen consisting of one daily pill (two participants in the lenacapavir group and nine participants in the daily pill group became infected) and much lower than the background HIV incidence. The most common adverse reactions, reported by at least 3% of people taking the drug, are nausea and injection-site reactions.
In the United States, the Food and Drug Administration (FDA) approved lenacapavir (SUNLENCA) in 2022 to treat HIV in people with multidrug-resistant infection whose current antiretroviral regimen is failing. In February 2025 the FDA accepted a new drug application for lenacapavir for HIV prevention under priority review. A decision is expected by June 19, 2025.
The FDA has approved two pills for daily use as PrEP; both are combinations of two HIV drugs in a single pill. Emtricitabine/tenofovir disoproxil fumarate (TRUVADA and generics) is for people at risk of HIV infection through sex or injection drug use. Emtricitabine/tenofovir alafenamide fumarate (DESCOVY) is for men at risk of getting HIV; it is not for women at risk through vaginal sex as its effectiveness for this purpose has not been studied. The FDA has also approved cabotegravir (APRETUDE), a long-acting injectable form of PrEP for people at risk for HIV through sex. Unlike lenacapavir, however, cabotegravir must be given every other month.
As has often been the case with effective HIV drugs, access to lenacapavir has been limited by the price ($42,000 per year). According to one estimate, lenacapavir could be made and sold at a profit if priced at $100 per year. The manufacturer has issued manufacturing licenses to six generics companies, and the drug should eventually become available in 120 mostly low- and lower-middle-income countries. The manufacturer, however, has bypassed the Medicines Patent Pool access process, excluded many countries (including most of South America), and created a needlessly complex licensing process.
Although long-acting injectable PrEP does not eliminate the need for a safe and effective HIV vaccine with a long-term immune response, it can change the course of the global HIV epidemic if it becomes widely available at reasonable cost and widely used — soon. This is yet another reason why the Trump Administration’s evisceration of the President’s Emergency Plan for AIDS Relief (PEPFAR) and the United States Agency for International Development (USAID), the main government agency implementing PEPFAR, is tragic and cruel.