Lenacapavir: The biannual injection that could change HIV prevention

In June 2025, the U.S. Food and Drug Administration (FDA) approved the first HIV preventive treatment administered with a single, semiannual injection. The drug, called lenacapavir , demonstrated 99.9% efficacy in preventing sexually transmitted HIV infection in clinical trials, marking a milestone in the fight against the virus that causes AIDS.

A daily pill to prevent

The preventive strategy in which HIV-negative people take antiretroviral medications to avoid infection if they are exposed to the virus is called PrEP (pre-exposure prophylaxis). It is indicated for those at higher risk, that is, people with multiple sexual partners who do not use condoms.

Since 2019, it has established itself as a key public health tool in Spain, although its effectiveness depends on adherence: until now, it required taking a daily pill. The arrival of new long-lasting options could change this scenario.

How does it work and how effective is it?

Lenacapavir belongs to a new class of antiretrovirals known as capsid inhibitors, designed to target the protein envelope that protects HIV and prevent the virus from replicating at multiple stages of its life cycle. Unlike daily pill-based PrEP , this drug is administered only twice a year via subcutaneous injection.

The results of clinical trials have been extremely encouraging. In two studies with thousands of participants from various groups, more than 99% of those who received lenacapavir remained HIV-free. In fact, one study recorded no infections among volunteers, while the other only detected two cases of infection. In other words, the biannual injection achieved practically 100% preventive efficacy, even higher than that of standard daily oral PrEP.

The magnitude of this breakthrough has been such that the prestigious journal Science singled out lenacapavir as one of the scientific breakthroughs of 2024.

Although daily oral PrEP has been available since 2019, many people are unable to use it: some due to medical contraindications, others because they lack easy access to services, and others because they struggle to maintain daily intake. The lack of alternatives to daily oral PrEP means that certain groups (for whom this option is not viable) are being left out of HIV prevention strategies.

Receiving just two injections a year to prevent HIV offers clear advantages over current methods. It improves adherence by avoiding the daily routine of taking pills or frequent visits to the health center, something especially useful for young people or people with access barriers. It also reduces stigma : by not having to carry visible medication, many find this option more private and discreet. Furthermore, by releasing the drug in a sustained manner, it guarantees continuous protection. This combination of convenience, effectiveness, and discretion may increase PrEP acceptance among those who currently do not use it.

However, lenacapavir only protects against HIV, so it must be combined with condom use and other preventive measures to avoid the transmission of other sexually transmitted infections.

Despite its potential, lenacapavir faces significant barriers to global implementation. Its price as a preventive tool makes it inaccessible to many health systems, especially in countries with fewer resources. Experts point out that it could be produced at a much lower cost, which has raised concerns among organizations such as UNAIDS , which warns that an innovation is only useful if it can reach those who need it.

Despite the scientific advancement represented by lenacapavir, its global access is at risk due to political and financial decisions. The discontinuation of PEPFAR funding by the U.S. government and cuts to the Global Fund have left the main mechanisms that could finance this innovation in low-income countries without financial support.

Gilead has signed voluntary licensing agreements with generic manufacturers for 120 low-income countries and has pledged to provide free access in the US for uninsured people, but many middle-income countries are still excluded. In addition to cost, logistical implementation will also be a challenge: administering an injection every six months requires health systems with tracking capacity, regular HIV testing, and trained personnel.

Gilead is already researching a once-a-year intramuscular version of lenacapavir, and is exploring self-injectable, insulin-like options to facilitate its use in areas with less healthcare access. The World Health Organization (WHO) has announced that it will publish guidelines on its use in July 2025, during the International AIDS Conference in Kigali . If current barriers are overcome, lenacapavir could usher in a new era of HIV prevention.

Ultimately, lenacapavir represents a momentous step forward in HIV prevention. With only two doses per year and outstanding efficacy, this new drug has the potential to be a game-changer in the fight against the epidemic, facilitating protection for populations that have so far faced barriers with existing strategies.

The great challenge from now on will be to ensure that its benefits reach all affected communities through equitable access policies and affordable prices. Only then can this scientific breakthrough translate into a real and lasting impact, bringing us one step closer to the goal of curbing HIV transmission worldwide.

Article presented in The Conversation .

Pablo Ryan Murúa: Professor of Medicine (Faculty of Medicine). Specialist in Internal Medicine (Infanta Leonor Hospital). Researcher (CIBERINFEC and IISGM), Complutense University of Madrid, and President of SEISIDA (Spanish Interdisciplinary AIDS Society).