A study called the PURPOSE 2 trial found that just two shots a year of lenacapavir can reduce the risk of HIV infection by 96%, proving it to offer near-total protection against HIV.
The PURPOSE 1 and PURPOSE 2 trials together showed that 99.9% of participants who received lenacapavir remained HIV negative.
To understand why those numbers matter, consider the scale of what they are up against. In 2024, 1.3 million people were newly infected with HIV. In 2024, someone died of HIV-related causes every single minute. There were globally 570 new HIV infections every day among young women and girls aged 15 to 24 in 2024 alone.
Existing prevention tools have made real progress since the early years of the epidemic. But they have not been enough, and a central reason for that failure is one of the most human problems in medicine: people do not take a daily pill every day.
Lenacapavir, now approved by the FDA under the brand name Yeztugo, changes that equation entirely. Two injections a year, six months apart, and you are protected. Science magazine named the drug its Breakthrough of the Year for 2024.
What lenacapavir actually is
Lenacapavir is not a new category of molecule in the same way that some drug breakthroughs are. It has been used since 2022 as a treatment for people living with HIV who had developed resistance to other antiretroviral drugs.
What the PURPOSE trials established was something different: that it could be used in people who are HIV-negative as pre-exposure prophylaxis, or PrEP, preventing infection before it occurs.
Lenacapavir is the first-in-class, long-acting HIV-1 capsid inhibitor, administered twice yearly via subcutaneous injection for pre-exposure prophylaxis in adults and adolescents weighing 35kg or more.
The word capsid refers to the protein shell that surrounds the HIV virus’s genetic material. That shell is critical to virtually every stage of the viral lifecycle: entry into cells, replication of the virus inside them, and the assembly of new viral particles that go on to infect other cells.
Lenacapavir targets the capsid protein, disrupting multiple stages of the viral lifecycle without cross-resistance to existing antiretrovirals. By targeting a completely different biological mechanism than earlier PrEP drugs, lenacapavir avoids the cross-resistance problem that has complicated treatment for people who have taken other antiretrovirals for years.
It is also engineered for long-acting release. A single subcutaneous injection into the abdomen, thigh, or upper arm releases the drug steadily over the following six months, maintaining protective concentrations in the body throughout that entire window.
How the trials were conducted
The PURPOSE 1 and PURPOSE 2 trials were large-scale, randomized, double-blind studies comparing twice-yearly lenacapavir to standard oral PrEP options.
PURPOSE 1 enrolled more than 5,000 cisgender women in sub-Saharan Africa, a population that carries an enormous and disproportionate share of new HIV infections globally.
PURPOSE 2 enrolled cisgender men, transgender women, transgender men, and gender-nonbinary persons at risk for HIV infection, and randomly assigned participants in a 2:1 ratio to receive subcutaneous lenacapavir every 26 weeks or daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF).
The comparison was against the current gold-standard oral PrEP medications, Truvada (F/TDF) and Descovy, which have been the primary prevention tools since 2012. The trial was not measuring lenacapavir against a placebo — it was measuring it against the best existing options.
Among the participants who received twice-yearly lenacapavir injections in PURPOSE 2, 99.9% did not acquire HIV, and only two participants acquired HIV.
Researchers found that adherence to lenacapavir injections was high, but adherence to oral Truvada and Descovy was low.
The problem this drug is actually solving
Pre-exposure prophylaxis with daily oral medications has been available in the United States since 2012. The science behind it is solid. When taken consistently, drugs like Truvada reduce the risk of sexually acquired HIV infection by approximately 99%. On paper, that is nearly as protective as lenacapavir.
In practice, the results have been dramatically weaker, because “when taken consistently” turns out to be a massive qualifier.
Around 3.5 million people were accessing PrEP in 2023, up from just 200,000 in 2017, but this remains far short of the 10 million target set for 2025. And of those 3.5 million, a significant proportion are not taking the medication every day as prescribed.
The barriers are real and they compound each other. Some people cannot remember a daily pill across months and years. Some face HIV-related stigma. Some face healthcare access gaps. And some face simple daily pill fatigue.
Two injections a year remove almost all of those barriers simultaneously. There is no daily pill to remember, carry, or explain. There is no pharmacy visit every month. There is no visible evidence of HIV-prevention behavior that could invite stigma. The protection is simply there, continuously, for six months at a time.
The part of this story that does not make the headlines
The drug that could, in theory, end new HIV infections is being sold in the United States for $28,218 per patient per year. While its production cost is estimated at just $25 per person annually, its market price in high-income settings represents roughly a thousand-fold markup.
That gap between what the drug costs to make and what it costs to buy is not an anomaly. It is the defining challenge of the entire lenacapavir story, and it maps directly onto the populations who need it most.
The world has been here before. In the early years of the AIDS crisis, effective antiretroviral treatment existed in wealthy countries while millions died in low-income ones. It took a decade of activist pressure, legal battles, and eventually generic manufacturing agreements to close that gap.
The access battle happening right now
Gilead Sciences, the manufacturer of lenacapavir, has signed licensing agreements with six generic drug manufacturers — including Dr. Reddy’s Laboratories and Hetero Labs of India — to produce affordable versions of the drug. Generic versions are to be made available at $40 per person per year in 120 low- and middle-income countries starting in early 2027, spearheaded by Unitaid, the Clinton Health Access Initiative, and the Gates Foundation.
But the 120-country coverage has significant gaps. Approximately 30% of HIV transmission happens in countries excluded from Gilead’s licensing agreement, including countries in South America, the Middle East, North Africa, and Central Asia — where the HIV epidemic has been growing fastest.
Additionally, the generic versions will not be available until 2027 at the earliest. UNAIDS modelling shows that if funding permanently disappears, there could be an additional 6 million HIV infections and 4 million AIDS-related deaths by 2029.
What the drug does inside the body
HIV relies on its capsid protein to execute a complex series of steps inside the human body. When the virus enters a cell, the capsid must disassemble at exactly the right time and in exactly the right location to release the viral genome. During replication, the capsid must reassemble with precise geometric precision. If either process is disrupted, the virus cannot complete its lifecycle.
Lenacapavir binds to a highly conserved site on the capsid protein — meaning a site that remains stable across different HIV strains because mutations at that site tend to be fatal to the virus itself.
The drug is formulated as nanoparticles that dissolve gradually in the subcutaneous tissue after injection, releasing therapeutic concentrations consistently over six months. Because protective levels are maintained continuously, there is no window of reduced protection that could be exploited by HIV exposure.
What comes after Yeztugo
Researchers are already investigating whether lenacapavir could be given as an annual injection rather than a twice-yearly one, with early pharmacokinetic trials underway.
There is also active research into combining lenacapavir with broadly neutralizing antibodies (bnAbs). Gilead is testing teropavimab and zinlirvimab as potential partners for lenacapavir in combination prevention and treatment regimens.
ViiV Healthcare, Gilead’s primary competitor in the long-acting HIV space, is also developing next-generation injectable agents, meaning the therapeutic landscape is likely to continue evolving rapidly.
What this changes about the conversation around HIV
Lenacapavir is the first tool that genuinely solves the adherence half of the HIV prevention equation. Two injections a year cannot be forgotten, stigmatized, or interrupted by pharmacy closures and prescription lapses.
What remains unresolved is the access half of the equation. A drug that could end the HIV epidemic, made available to wealthy countries for $28,000 a year and to the highest-burden countries for $40 starting in 2027 — while a third of transmission hotspots remain outside the licensing agreement entirely — is not a solved problem.
It is a solved scientific problem sitting inside an unsolved political and economic one. The science has delivered what it was asked to deliver. The question of whether this moment will be defined by its discovery, or by what was done to put it in the hands of everyone who needed it, is still being written.
Sources:
- PURPOSE 2 Trial. New England Journal of Medicine. 2025. DOI: 10.1056/NEJMoa2411858
- FDA approves twice-a-year injection for HIV prevention. CNN. June 18, 2025.
- WHO recommends highly effective, twice-yearly shot for prevention. Healthline. July 14, 2025.
- Lenacapavir and global HIV prevention: a breakthrough at risk of leaving millions behind. PMC. February 2026.
- Twice-Yearly Injectable PrEP With Lenacapavir. PMC. 2025.
- Agreements to provide affordable lenacapavir. The Lancet Microbe. January 2026.
- Adepoju VA, Abdulrahim A. International Journal for Equity in Health. October 2025.
- UNAIDS Global AIDS Update 2025.
- UNAIDS Fact Sheet 2025: Global HIV Statistics.
- NIH ClinicalInfo. Lenacapavir HIV Prevention Health Professional Drug Record.
