For decades, one of the most effective ways to prevent HIV has depended on a deceptively difficult routine: taking a tablet every day, even when life is busy, uncertain, or far from home.
That routine is changing. In 2025, the U.S. Food and Drug Administration approved lenacapavir, sold for prevention under the brand name Yeztugo, as the first HIV pre-exposure prophylaxis, or PrEP, option given twice a year. The medicine is designed for adults and adolescents who weigh at least 35 kilograms and are at risk of acquiring HIV.
The approval does not mean HIV prevention has become effortless, universal, or finished. People still need HIV testing, clinical care, and protection against other sexually transmitted infections. Access, cost, stigma, and the practical challenge of reaching a clinic every six months will all shape the medicine’s real-world impact.
But lenacapavir represents a significant shift in the design of prevention. It moves PrEP from a daily reminder on a phone or bedside table to an occasional appointment—and, in large clinical trials, it showed an extraordinary ability to prevent HIV infection when administered as directed.
The adherence problem behind the breakthrough
Daily oral PrEP already works extremely well when taken consistently. The difficulty is not simply whether a medicine can block HIV. It is whether people can keep using it during changing relationships, travel, financial stress, concerns about privacy, unstable housing, or ordinary forgetfulness.
Those barriers are especially important because HIV exposure is not evenly distributed around the world. Prevention needs to work for people whose lives do not fit neatly into a regular medical schedule. A person may want protection but not want family members, partners, or housemates to see a bottle of pills. Someone else may find a six-month clinic visit easier than a daily medication routine.
Lenacapavir offers another choice. It belongs to a class of medicines called capsid inhibitors. Rather than targeting the virus in exactly the same way as older antiretroviral drugs, it interferes with the HIV capsid, the protein shell that helps the virus protect and organize its genetic material. By disrupting several stages of the viral life cycle, lenacapavir can prevent HIV from successfully establishing an infection.
The drug’s chemistry also helps explain its unusual schedule. Lenacapavir remains in the body for a long time. For prevention, the approved regimen begins with oral tablets, followed by two injections under the skin of the abdomen. The injections are repeated every six months by a health professional.
What the major trials found
The strongest early evidence came from PURPOSE 1, a large randomized trial conducted among cisgender adolescent girls and young women in South Africa and Uganda. The trial compared twice-yearly lenacapavir with two daily oral PrEP options: tenofovir alafenamide with emtricitabine, and tenofovir disoproxil fumarate with emtricitabine.
No participants who received lenacapavir acquired HIV during the trial. The study included more than 5,000 participants overall, with more than 2,000 assigned to the lenacapavir group. Researchers reported that the injection was superior to the background HIV incidence expected in the study population and superior to the daily oral comparison group.
The result was notable for both biological and practical reasons. It showed that the drug could protect against HIV, but it also reduced dependence on daily adherence. Participants did not have to make a visible or repeated decision every day. The prevention was built into two planned clinical visits each year.
A second major study, PURPOSE 2, tested lenacapavir among cisgender men and gender-diverse people in several countries, including the United States, Argentina, Brazil, Mexico, Peru, South Africa, and Thailand. In that trial, two participants in the lenacapavir group acquired HIV among more than 2,000 people who received the injections. Researchers estimated efficacy at roughly 99.9 percent compared with the expected HIV incidence in the study population.
These studies involved different populations and settings, so their results should not be flattened into one universal number. Clinical trials are carefully organized, participants receive counseling and testing, and follow-up is closely monitored. The results nevertheless point in the same direction: a long-acting option can provide very high protection while addressing one of the central weaknesses of daily PrEP.
Why twice-yearly prevention matters
The public-health promise of lenacapavir is not only that it is powerful. It is that it may make prevention more compatible with how people actually live.
Daily pills can be highly effective, but their success depends on regular use. A missed dose is not automatically a failure, and the level of protection varies according to the type of exposure and the pattern of use. Still, repeated interruptions can reduce protection and make it harder for clinicians to know whether a person is covered.
An injection given every six months changes that calculation. It can reduce the number of medication decisions, help people maintain protection during periods when daily pills are difficult, and offer a more discreet option for those worried about being identified as someone who uses PrEP.
The benefit may be particularly important in regions where HIV incidence remains high among young women and other groups facing unequal access to prevention. PURPOSE 1’s results in South Africa and Uganda are therefore more than a technical demonstration. They show how a prevention method can be designed around communities that have often carried a disproportionate share of the HIV epidemic.
There is also a broader lesson. Medical progress is sometimes measured by a new molecule or a stronger laboratory result. But a medicine can be transformative because it changes the work required from the person using it. Six months is a different kind of commitment from every day.
The safeguards are part of the treatment
Lenacapavir is not an HIV vaccine, and it does not treat an existing HIV infection. Before each injection, people must be tested to confirm that they do not have HIV. The reason is important: if someone acquires HIV while receiving a prevention drug alone, the virus may be exposed to an incomplete treatment regimen, which can encourage drug resistance.
People beginning PrEP also need appropriate testing for recent infection, including attention to symptoms and other testing methods when clinically indicated. If HIV is diagnosed, the person needs a complete combination treatment regimen rather than prevention-only medication.
The injections do not prevent other sexually transmitted infections, including syphilis, gonorrhea, or chlamydia. Condoms, testing, vaccination where available, and regular sexual-health care remain useful. Prevention works best when people can choose from several tools rather than being told that one method must fit everyone.
There are practical considerations as well. A twice-yearly injection requires reliable follow-up. If a scheduled dose is delayed, clinicians need a plan to maintain protection, which may include oral medication. Injection-site reactions were reported in clinical studies, as can happen with injectable medicines. Most were manageable, but people and providers will need clear information about what to expect.
Approval is the beginning of access—not the end
The FDA decision establishes a new option in the United States, but approval alone does not determine who will receive it. Price, insurance coverage, public-health purchasing, clinic capacity, transportation, and the availability of trained providers will influence uptake.
There is also a global-access question. The populations who could benefit most from long-acting prevention are not always the populations best served by existing health systems. A medicine that requires a clinic visit twice a year may be easier than daily pills for some people, but it still depends on clinics, supply chains, laboratory testing, and respectful care.
Gilead Sciences, which developed lenacapavir, has announced licensing arrangements intended to support lower-cost generic production for many lower-income countries after regulatory steps are completed. The details of availability, pricing, and timing will vary by country. That uncertainty is a reminder that scientific success and public-health success are related but not identical achievements.
A new rhythm for prevention
HIV prevention has advanced through layers of protection: condoms, testing, treatment that prevents transmission, daily PrEP, and emergency post-exposure medication. Lenacapavir adds a long-acting option to that expanding toolkit.
Its most important contribution may be simple to describe. Instead of asking people to remember protection every day, it gives them the possibility of planning protection around two appointments a year.
That change will not eliminate HIV, and it will not remove the need for trust, education, funding, or accessible care. But it shows what happens when medical innovation responds not only to the biology of a virus, but also to the realities of human behavior.
For millions of people who want protection but struggle with daily medication, a twice-yearly injection could make prevention feel less like a constant task and more like a dependable part of ordinary healthcare. That is a meaningful step forward—and one that may help bring the end of HIV transmission closer within reach.