On June 18, 2025, the Food and Drug Administration approved twice-yearly lenacapavir for pre-exposure prophylaxis (PrEP), making it the longest-acting HIV prevention method. While clinicians, advocates, and people at risk for HIV are excited about this new option, many are worried that the drug’s high price tag could limit access as funding for HIV prevention is slashed in the United States and worldwide.

“This long-acting injectable PrEP option could be a game-changer in HIV prevention,” said San Francisco AIDS Foundation medical director Hyman Scott, MD, MPH. However, if the cost is too high, “it won’t be accessible and affordable for all who want it. At a time when HIV prevention is deprioritized by the federal government, no-cost coverage for preventive medications is at risk, and HIV research is in jeopardy, we need these new preventive tools more than ever.”

Lenacapavir, Gilead Sciences’ HIV capsid inhibitor, is an antiretroviral drug that blocks viral replication. It is not a vaccine that trains the immune system to fight the virus, but after all traditional HIV vaccine candidates have failed in clinical trials to date, long-acting PrEP is the next best thing.

Lenacapavir was initially approved in 2022 under the brand name Sunlenca for use as part of a combination antiretroviral regimen for heavily treatment-experienced people with multidrug-resistant HIV. Lenacapavir for PrEP got a new brand name—Yeztugo—and a price reduction from about $42,000 to $28,218 per year.

The approval of lenacapavir for PrEP comes 13 years after the FDA approved the first biomedical HIV prevention option, Gilead’s once-daily Truvada pill (tenofovir disoproxil fumarate/emtricitabine). Gilead’s Descovy pill (tenofovir alafenamide/emtricitabine) was approved for HIV prevention for certain populations in 2019. ViiV Healthcare’s Apretude (injectable cabotegravir), which is administered every other month, was previously the longest-acting PrEP option.

Yet biomedical HIV prevention has still not reached its full potential. According to the latest surveillance data from the Centers for Disease Control and Prevention (CDC), more than 39,000 people were newly diagnosed with HIV in 2023. But the CDC has estimated that only around a third of the 1.2 million or more people who could benefit from PrEP are using it. Experts are hopeful that a twice-yearly option could help close the gap.

“Yeztugo could be the transformative PrEP option we’ve been waiting for—offering the potential to boost PrEP uptake and persistence and adding a powerful new tool in our mission to end the HIV epidemic,” Carlos del Rio, MD, of Emory University School of Medicine, said in a Gilead news release. “A twice-yearly injection could greatly address key barriers like adherence and stigma, which individuals on more frequent PrEP dosing regimens, especially daily oral PrEP, can face.”

While daily PrEP pills are around 99% effective when taken consistently, other options are still needed. Some people have trouble remembering to take a pill every day, feel stigma around using antiretrovirals or are in living situations where their pill bottles could be lost or stolen. In addition, oral PrEP users require routine monitoring that involves clinic visits every three months.

Twice-yearly PrEP could be particularly beneficial for people who face more barriers to taking daily pills, including those with mental health or substance use issues and those experiencing homelessness or unstable housing.“I am excited about the highly anticipated approval of long-acting lenacapavir for HIV prevention as our data and that of others have shown that long-acting PrEP works well for people who have concomitant challenges such as housing insecurity and substance use,” said Monica Gandhi, MD, MPH, medical director of the Ward 86 HIV Clinic at San Francisco General Hospital. “We saw higher rates of retention on long-acting cabotegravir PrEP than on oral PrEP in a population with such challenges and anticipate that long-acting lenacapavir will similarly be very effective for people at risk for HIV.”

Highly Effective in Studies

The FDA approval is supported by two large studies showing that lenacapavir PrEP dramatically reduced HIV acquisition in groups at high risk. Results from the Phase III PURPOSE 1 trial, first presented at last year’s International AIDS Conference, showed that twice-yearly lenacapavir PrEP was 100% effective for young cisgender women in Africa. The twice-yearly injections significantly reduced HIV incidence compared with the background rate and were superior to daily Truvada pills. Several studies have found that injectable antiretrovirals encourage better adherence among women.

Results from the PURPOSE 2 study, presented at the HIV Research for Prevention Conference last October, showed that lenacapavir injections every six months reduced the risk of HIV acquisition by 96% relative to background incidence and by 89% compared to Truvada for gay and bisexual men and gender-diverse people in the United States and six other countries. In both trials, lenacapavir injections were safe and generally well-tolerated.

The FDA approved Yeztugo for adults and adolescents to reduce the risk of sexually acquired HIV. People who wish to start lenacapavir PrEP must first have a negative HIV test. The regimen involves an initiation dose of lenacapavir pills for the first two days along with two subcutaneous injections administered by a health care provider. After that, two more injections are given together every six months.

Long-acting PrEP may also reduce the risk of HIV acquisition via shared drug injection equipment. The smaller Phase II PURPOSE 4 trial is currently evaluating lenacapavir PrEP for people who use drugs. Another study, PURPOSE 3, is testing the regimen for cisgender women in the United States.

“The FDA approval of lenacapavir is a fitting culmination of a long journey of drug discovery and development,” said PURPOSE 2 investigator Onyema Ogbuagu, MBBCh, of Yale School of Medicine. “The excellent results we observed with twice-yearly lenacapavir provide renewed optimism about how far we could go with our new biomedical tools to achieve greater uptake of HIV prevention to help us move closer to ending the HIV epidemic.”

But the journey may not be over yet, as early research suggests that once-yearly prevention shots might be enough. At this year’s Conference on Retroviruses and Opportunistic Infections, Gilead scientists reported that longer-lasting formulations of lenacapavir produced drug concentrations even higher than those of twice-yearly administration.

Access Is Key

To have a real impact on the HIV epidemic, though, advocates and health officials stress that long-acting lenacapavir PrEP must be widely available and affordable to those who need it most in the United States and worldwide. But access is threatened by the Trump administration’s proposed budget, which decimates funding for HIV prevention services, particularly those targeting groups at higher risk for HIV, including Black and Latino gay men and transgender women. Deep cuts to Medicaid in the proposed House and Senate budgets are also a concern, as some 40% of people with HIV rely on the public insurance program.

“We are hopeful about the impact of this new method of PrEP on reducing HIV transmission and disparities in PrEP uptake both domestically and globally. However, there are many challenges in the current environment that must be overcome in order to ensure equitable access and affordability,” said Anne Donnelly, SFAF’s director of state health care policy. “Cuts to Medicaid and Affordable Care Act premium subsidies included in Trump’s ‘Big, Beautiful Bill,’ if adopted, will result in the loss of coverage for millions across the nation and loss of access to preventive services for many of those most at risk for HIV. The defunding of both global and domestic HIV prevention and barriers to access from insurers are also a significant concern.”

Under the Affordable Care Act, insurers must cover recommended prevention services at no charge, a requirement the Supreme Court upheld last week in the Braidwood case. But at $14,109 per shot, Yeztugo is priced much higher than the approximate $30 monthly cost for generic versions of Truvada, so insurers may ask people to try the daily pills first or attempt to avoid covering lenacapavir PrEP altogether.

“Although the total cost of lenacapavir per year is not that different than the total cost of long-acting cabotegravir for PrEP, these are days of austerity in health care, including the concerning possibility of a $1 trillion cut to Medicaid, leaving the health insurance program for low-income individuals in the U.S. severely underfunded,” Gandhi said. “Trump’s America in 2025 is very different than the landscape for health insurance coverage in 2021 when long-acting cabotegravir was approved. I am very worried that large health insurance carriers will not approve lenacapavir on their formularies at this proposed price point and urge [Gilead] to reconsider their price to improve access to lenacapavir for Americans.”

At the global level, broad access to lenacapavir is threatened by the Trump administration’s cuts to PEPFAR, the President’s Emergency Plan for AIDS Relief, which has been the largest funder of PrEP worldwide. Although officials have claimed that that HIV treatment funding would continue, the status of prevention services is uncertain.

Gilead’s strategy for lenacapavir PrEP in the U.S. “is designed to enable broad uptake and availability for individuals with and without insurance coverage,” the company said in a statement. Gilead is working with insurers to encourage coverage and offers co-pay assistance for out-of-pocket costs and a patient assistance program for low-income uninsured or underinsured people. Outside the U.S., the company announced last year that it will work with several pharmaceutical manufacturers to offer generic versions of lenacapavir PrEP in more than 100 lower-income countries, providing the drug at no profit until generic manufacturers are up and running in countries with the highest HIV rates. But advocates argue that middle-income countries such as Brazil—one of the countries where PURPOSE 2 was conducted—also need access to lenacapavir PrEP at an affordable cost.

“The FDA approval of lenacapavir is a game-changer for HIV prevention,” said International AIDS Society president Beatriz Grinsztejn, cofounder of the Fiocruz HIV/AIDS Service in Rio de Janeiro. “This twice-yearly injection expands the prevention toolkit by easing the burden of daily adherence, reducing stigma and alleviating pressure on healthcare systems. However, for lenacapavir to make a difference, it must be affordable and accessible globally, particularly for the most vulnerable populations.”