WHO Adds Lenacapavir to Its HIV PrEP Recommendations Amid Underutilization of PrEP and Severe PEPFAR Funding Cutbacks | IAS 2025

As expected, the new recommendations that the World Health Organization (WHO) issued for HIV and sexually transmitted diseases add lenacapavir preexposure prophylaxis (PrEP) to its list of prevention options. Lenacapavir for PrEP requires only two subcutaneous shots per year. Its efficacy and dosing schedule have stirred a cross-current of hope as the Trump administration has pulled back funding for HIV prevention in sub-Saharan Africa and elsewhere. .

WHO posted the HIV recommendations online early in the day. WHO officials presented and discussed the recommendations during a session with an overflow audience at the International AIDS Society meeting in Kigali, Rwanda.

Health officials say PrEP is underutilized around the world, a situation that could get worse with the Trump administration’s pullback of funding of the U.S. President’s Emergency Plan for AIDS Relief, better known by its acronym, PEPFAR. PEPFAR has funded most of the initial doses of PrEP globally and has played a large role in HIV prevention and treatment in sub-Saharan Africa. The Trump administration has allowed PEPFAR to continue funding treatment programs but has effectively eliminated funding for prevention programs other than those for pregnant and breastfeeding women.

Meg Doherty, M.D., M.P.H., Ph.D., of the WHO, right, after the IAS session on the World Health Organization's lenacapavir and other HIV recommendations.

“PrEP is not being used to its full potential,” said Meg Doherty, M.D., M.P.H., Ph.D., director of the Department of Global HIV, Hepatitis and Sexually Transmitted Infections Programmes at WHO and the leader of the organization’s recommendations effort. Oral PrEP was used by about 3.9 million people in 2024, far short of a 2025 target of 21.2 million people, according to an update report issued last week by the Joint United Nations Programme on HIV and AIDS (UNAIDS).

Lenacapavir for PrEP was approved by the FDA on June 18 based on clinical trials showing that it is almost 100% effective at preventing HIV infection. It is not the only long-acting form of PrEP, but the dosing schedule for long-acting injectable cabotegravir (CAB LA), sold under the brand name Apretude, is every eight weeks after initial doses, and the injections are intramuscular.

Lenacapavir for PrEP was developed by Gilead Sciences, which is marketing it under the brand name Yeztugo, but in global health circles it is known by its generic name, which often gets shortened to len or LEN.

The WHO’s lenacapavir recommendation is its latest for different forms of PrEP that started with a 2015 recommendation for oral PrEP containing tenofovir disoproxil fumarate (TDF), followed by a 2021 recommendation for the dapivirine ring and a 2022 recommendation for long-acting injectable cabotegravir (CAB-LA). The WHO recommendations are additive and don’t indicate a preference of one form of PrEP over another.

“What is important is choice,” said Michelle Rodolph, a WHO technical officer who made the point that people are more likely to use PrEP if they have a number of approaches to select from.

The new WHO recommendations also advise the use of rapid diagnostic tests for initiation, continuation and discontinuation of long-acting PrEP. Testing is a critical aspect of PrEP programs because people who test positive would be referred for treatment rather than be prescribed PrEP. But the WHO recommendations stop short of recommending HIV self-testing of long-acting PrEP. Some HIV researchers and advocates see self-testing as a cost-effective way to expand testing and antiretroviral therapy for those who need it.

The news release issued by WHO today about the lenacapavir was enthusiastic about the new form of PrEP. “With just two doses per year, LEN is a transformative step forward in protecting people at risk of HIV—particularly those who face challenges with daily adherence, stigma, or access to health care,” it said.

Global Fund deal

But in addition to the cutback of PEPFAR funds, issues of price, procurement and licensing sow concern into the optimism about lenacapavir for PrEP. Gilead has said it will supply lenacapavir at no profit to itself until generic versions are available and that it has signed royalty-free licensing agreements with generic manufacturers. Last week, the company and The Global Fund to Fight AIDS, Tuberculosis and Malaria (the Global Fund) announced they had signed an “access agreement” for the Global Fund to procure lenacapavir. Gilead said in its news release that the company will supply enough doses to reach up to two million people over three years in countries supported by the Global Fund. The Global Fund heralded the agreement as marking the first time that an HIV prevention product will be available in low- and middle-income countries as well as high-income countries.

Other WHO recommendations

The recommendations issued by WHO today touched on a range of HIV issues. A set of treatment guidelines changed a preference for tenofovir disoproxil fumarate (TDF) for antiretroviral therapy to making tenofovir alafenamide (TAF) an equal alternative choice. In an interview, Lloyd Mulenga, M.B.Ch.B., Ph.D., an infectious disease and internal medicine specialist at the University Teaching Hospital in Lusaka, Zambia, and Director of Infectious Diseases for Zambia’s Ministry of Health, said leveling TDF and TAF is important. TDF has bone and kidney side effects that can pose a problem in the HIV treatment population that is aging. Mulenga said that his country, Botswana and Zimbabwe had already switched to TAF antiretroviral therapy, which has the advantage of being a smaller tablet than TDF.

Other WHO recommendations issued today include:

• Dolutegravir-3TC, marked under the name Dovato, can be used for “treatment simplification” for adults and adolescents with undetectable HIV viral load on three-drug antiretroviral regimens and without active hepatitis B infection.
• Long-acting injectable cabotegravir and rilpivirine, sold under the brand name Cabenuva, can be used as an alternative switching option for adults and adolescents with undetectable HIV viral load on oral antiretroviral therapy and without active hepatitis B infection.
• When national programs recommend replacement feeding, mothers living with HIV who are receiving antiretroviral therapy and have suppressed viral loads should be offered the choice to breastfeed and “be supported in their infant feeding choice,” say the recommendations. They also suggest support interventions be offered to mothers living with HIV who are breastfeeding to optimize antiretroviral adherence.
• Diabetes, hypertension care, mental health, and alcohol use disorders should be integrated with HIV services.