[Update: On September 18, 2025, the Centers for Disease Control and Prevention added lenacapavir to its recommendations for HIV pre-exposure prophylaxis.]

[Update: On July 25, 2025, the European Medicines Agency recommended marketing authorization for lenacapavir PrEP in the European Union, where it will be marketed under the brand name Yeytuo.]

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On June 18, the Food and Drug Administration (FDA) approved twice-yearly lenacapavir for pre-exposure prophylaxis (PrEP), making it the longest-acting approved HIV prevention option. Advocates lauded the eagerly anticipated approval but expressed concern that the $28,000 annual price tag could limit access as HIV prevention funding is being slashed in the United States and worldwide.

“The approval of lenacapavir is a much-needed boost for HIV prevention, given the strength of the science and the simultaneous disruption in HIV programs globally,” said Mitchell Warren, executive director of AVAC, in a statement. “But U.S. FDA approval is just one in a series of steps needed to ensure that injectable lenacapavir can help reduce the 1.3 million new HIV infections that occur each year. Scientific progress only matters if innovation actually reaches people. Lenacapavir for PrEP is poised to reshape the HIV response but only if today’s approval is accompanied by bold, strategic, effective and equitable rollout that reaches the populations that need access.”

Lenacapavir, the first 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 studies to date, long-acting PrEP is the next best thing.

Lenacapavir was approved in 2022 under the brand name Sunlenca to be used in combination regimens for treatment-experienced people with multidrug-resistant HIV. Lenacapavir for PrEP, which is used alone, was given a new brand name—Yeztugo—and a price reduction from about $42,000 per year.

Today’s approval comes 13 years after the FDA approved the first PrEP option, Gilead’s once-daily Truvada pill (tenofovir disoproxil fumarate/emtricitabine). Gilead’s Descovy pill (tenofovir disoproxil fumarate/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. 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.

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, up from about 38,000 the year before. The CDC estimates that only around a third of the 1.2 million people who could benefit from PrEP are using it; a more recent analysis suggests that the unmet need could be even greater. In particular, PrEP uptake has been lower among Black and Latino gay and bisexual men and among women. But biannual PrEP injections 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,” said Carlos del Rio, MD, of Emory University School of Medicine, 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.”

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 the 2024 International AIDS Conference and published in The New England Journal of Medicine, showed that twice-yearly lenacapavir PrEP was 100% effective for young cisgender women in Africa. The injections significantly reduced HIV incidence compared with the background rate and were superior to daily Truvada pills. Several studies have found that injectable antiretrovirals can encourage better adherence among women.


Results from the PURPOSE 2 study, presented at the HIV Research for Prevention Conference last October and also published in The New England Journal of Medicine, 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.

Based on these findings, the FDA approved Yeztugo for adults and adolescents to reduce the risk of sexually acquired HIV. People seeking 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, followed by two more injections every six months.

Long-acting PrEP may also reduce the risk of HIV acquisition via shared drug injection equipment. PURPOSE 3 and PURPOSE 4, two smaller Phase II studies evaluating lenacapavir PrEP for cisgender women and people who use drugs in the United States, are now underway.

“The FDA approval of lenacapavir is a fitting culmination of a long journey of drug discovery and development,” PURPOSE-2 investigator Onyema Ogbuagu, MBBCh, of Yale School of Medicine, told POZ. “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: Early research suggests that, in the future, once-yearly prevention shots might be enough. At the Conference on Retroviruses and Opportunistic Infections in March, Gilead scientists reported that longer-lasting formulations of lenacapavir produced drug concentrations even higher than those of twice-yearly administration.

Access Is Key to Ending the Epidemic

To have a real impact on the epidemic, however, advocates and health officials stress that long-acting PrEP must be widely available and affordable to those who need it most in the United States and worldwide.

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

In a statement to POZ, Gilead said its access strategy for lenacapavir PrEP in the United States “is designed to enable broad uptake and availability for individuals with and without insurance coverage.” The company 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.

Under the Affordable Care Act, insurers are required to cover recommended prevention services at no charge. 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. What’s more, the Supreme Court is currently considering a legal challenge lodged by conservative businesses that object to mandated PrEP coverage on religious grounds. A decision in the Braidwood case is expected this month.

The Trump administration’s proposed budget includes drastically reduced funding for HIV prevention, which advocates fear could curtail PrEP provision.

“Recent actions by the Trump administration to decimate HIV prevention jeopardize access to preventive measures such as PrEP,” said Carl Schmid, executive director of the HIV+Hepatitis Policy Institute. “In fact, the president’s budget zeroes out all CDC HIV prevention and surveillance funding, hampering our nation’s ability to make people aware of and access new HIV prevention measures. Dismantling these programs means that there will be a weakened public health infrastructure and much less HIV testing, which is needed before a person can take PrEP.”

Deep cuts to Medicaid in proposed House and Senate budgets are also a concern, as some 40% of people with HIV rely on the public insurance programs.

“The long-anticipated approval of lenacapavir as a once every six month injectable option for PrEP is a welcome development in the fight to end HIV as an epidemic. It is also a testament to the value and power of American taxpayer investment in the research at the National Institutes of Health that set the stage for this groundbreaking advancement,” the advocacy group PrEP4All said in a statement. “However, the path to access is more perilous than ever for the communities in greatest need of PrEP, and it is far from clear that innovation will triumph over the expensive price Gilead has set for lenacapavir coupled with active efforts by the Trump administration and congressional Republicans to dismantle HIV prevention and health care systems in America.”

“The FDA’s approval of lenacapavir for HIV prevention has the potential to be a pivotal moment for the broader fight to end HIV,” added Maxx Boykin, manager of the Save HIV Funding campaign. “It’s a reminder that prevention must be a national priority, backed by serious investment and political will. Ending the epidemic requires equal focus on prevention and treatment, delivered through equitable, community-driven systems. This moment calls for bold public funding, strong private sector leadership and a shared commitment to making HIV prevention accessible, affordable and a cornerstone of our national response.”

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 Secretary of State Marco Rubio has said that HIV treatment funding would continue, the status of prevention services is uncertain. Regulatory authorities in Canada, Europe, Brazil, Australia and South Africa are reviewing lenacapavir PrEP for approval, and the World Health Organization is expected to release updated PrEP guidelines in July. 

Gilead 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 itself at no profit until generic manufacturers are up and running in countries with the highest HIV rates. A study presented at last year’s International AIDS Conference found that the price of lenacapavir could be brought down to around $40 per year with voluntary licensing and competition between generic suppliers. 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.

“Lenacapavir could be the tool we need to bring new infections under control—but only if it is priced affordably and made available to everyone who could benefit,” UNAIDS executive director Winnie Byanyima said in a statement. “If this game-changing medicine remains unaffordable, it will change nothing. I urge Gilead to do the right thing. Drop the price, expand production and ensure the world has a shot at ending AIDS.”

[This report has been updated to add comments from advocates.]

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