Opinion column: lenacapavir, a major milestone in the fight against HIV

By Prof. Yazdan Yazdanpanah, Director of ANRS MIE, and Prof. Jean-Michel Molina, université de Paris Cité and APHP.

Last updated on 25 June 2025

The US Food and Drug Administration (FDA) has approved the twice-yearly subcutaneous lenacapavir as HIV pre-exposure prophylaxis (PrEP). This drug, developed by the American laboratory Gilead Sciences, is a major breakthrough in the fight against HIV and helps to significantly reduce the risk of sexually acquired HIV in adults and adolescents. Because of its administration route, lenacapavir is a medical breakthrough to prevent HIV infections, offering hope to millions of people who have difficulty taking daily oral preventive medications.

FDA approval of lenacapavir is a crucial step in our fight against HIV. This treatment could revolutionise prevention and offer new protection to vulnerable populations

Prof. Yazdan Yazdanpanah, Director of ANRS MIE

This approval is released just one year after preliminary findings from the PURPOSE 1 trial, conducted in South Africa and Uganda, which showed very significant efficacy in preventing HIV in adolescent and adult cisgender women (1).
The efficacy was confirmed six months later by PURPOSE 2, conducted among gay and bisexual men, and trans and non-binary people in several countries, including the United States, South Africa, Peru, Brazil, Mexico, Argentina and Thailand (2).

Additional trials (PURPOSE 3, 4 and 5) are ongoing in different populations and countries, including France for PURPOSE 5, the first trial in Europe using this HIV prevention treatment.

PURPOSE 1 and PURPOSE 2 findings are very promising. They show that a preventive drug administered just twice yearly is able to prevent HIV infection very effectively in people who are at risk and do not use condoms

Prof. Jean-Michel Molina, université de Paris Cité and AP-HP

Lenacapavir adds to the existing PrEP treatments, available in oral form (tenofovir/emtricitabline) taken daily or on demand (at the time of sexual intercourse). This new injectable PrEP, which only needs to be given twice a year, could be a ‘’game changer’’ in the HIV epidemic, just as antiretroviral treatments were in 1996. Its long-acting nature – currently six months, but soon to be a year – could make it easier for users to adhere to the drug and stick with it. Another injectable PrEP drug, cabotegravir, has already been approved in the United States and Europe, and should soon be available in France. Cabotegravir is administered as two intramuscular injections every two months.

However, despite the hopes raised by lenacapavir and its approval by the FDA, a number of research questions need to be answered. It is crucial to study issues related to implementation across populations and countries, pharmacology, access and equity, particularly in low- and middle-income countries. These studies are all the more important, especially in the current context of dramatic cuts in funding and international cooperation.

“It is essential not to overlook the practical and economic challenges of implementing this treatment. We need to ensure that lenacapavir is accessible to all, regardless of countries’ financial resources,

Prof. Yazdan Yazdanpanah, Director of ANRS MIE.”

To prepare for lenacapavir rollout in France, ANRS MIE created a working group a few months ago, coordinated by Professor Jean-Michel Molina, principal investigator of the two pivotal PrEP trials in France (ANRS Ipergay, launched in 2012, and ANRS Prévenir launched in 2017)(3,4). The task of this working group, which brings together community representatives and multidisciplinary researchers working in different countries, is to define the research questions raised by the arrival of long-acting preventive treatments, and to develop implementation projects in different populations, territories and countries.

“Our working group is determined to identify the best strategies for incorporating lenacapavir into existing prevention programmes. We are collaborating with international experts to ensure a global and inclusive approach,

Prof. Jean-Michel Molina, université de Paris Cité and APHP.”

The results will help to guide public authorities when drawing up recommendations on the rollout of this new PrEP. It is therefore urgent to initiate this work as soon as possible, by facilitating lenacapavir availability to conduct “real-life” research. ANRS MIE is fully committed to this approach, working with political and health authorities to make this innovation a reality accessible to all.

In conclusion, lenacapavir is a ‘’game changer’’ in the fight against HIV. In collaboration with experts and community representatives, ANRS MIE is determined to play a key role in the implementation of this scientific breakthrough.

References

  1. Behkker LG, et al. Twice-yearly lenacapavir or daily F/TAF for HIV prevention in cisgender women. N Engl J Med 2024;391(13):1179-1192.
  2. Kelley CF, et al. Twice-yearly lenacapavir for HIV prevention in men and gender-diverse persons. N Engl J Med 2025;392(13):1261-1276
  3. Molina J-M, et al. On-demand preexposure prophylaxis in men at high risk for HIV-1 infection. N Engl J Med 2015;373(23):2237-46.
  4. Molina J-M, et al. Daily and on-demand HIV pre-exposure prophylaxis with emtricitabine and tenofovir disoproxil (ANRS PREVENIR): a prospective observational cohort study. Lancet HIV 2022;9(8):e554-e562.