HIV transmission prevented 100% by twice-yearly lenacapavir injection in trial

A pair of late-stage clinical trials testing a long-acting injectable for HIV prevention produced results that stunned researchers: almost no new infections among thousands of participants. The drug, lenacapavir, given as a subcutaneous shot twice a year, delivered protection levels that rival — and in practical terms may outperform — daily oral PrEP options.

These findings have immediate public-health implications for countries with high HIV incidence rates, and they could change how prevention programs are delivered worldwide. Below, the trial findings, how the drug works, and what this could mean for access and stigma are explained in detail.

Major trial results: near-total prevention of HIV transmission

Two phase 3 studies, known as PURPOSE 1 and PURPOSE 2, tested lenacapavir injections as pre-exposure prophylaxis (PrEP). The trials used rigorous randomized, double-blind methods, not against a placebo but versus the current standard of care — daily oral PrEP (Truvada or Descovy).

PURPOSE 1: Young women in high-incidence settings

• PURPOSE 1 enrolled about 3,200 participants, focused mainly on young women in high-HIV-incidence countries such as Uganda and South Africa.
• Participants received lenacapavir injections every six months and were monitored for HIV infection.
• Over the study period the injection arm reported no new HIV infections, a finding described by investigators as extraordinary.

PURPOSE 2: Broader population, across more countries

• PURPOSE 2 expanded the geographic reach and participant mix to include men and people of different ages, with a total enrollment near 5,000.
• The study again compared twice-yearly lenacapavir to daily oral PrEP and found a reduction in infections of approximately 99.9%.
• Both trials were stopped early for ethical reasons once the benefit of the injectable was clear to investigators and oversight boards.

How the trials were run and why they were stopped early

Both studies were designed as randomized and double-blinded, but they did not include a true placebo group; instead researchers compared the long-acting injection to established oral PrEP therapies. Daily oral options like Truvada and Descovy have shown very high efficacy when taken consistently — approaching 99.9% protection in clinical development — but that level of protection depends on strict adherence.

Investigators cited adherence, equity, and participant welfare when halting the trials early. Because the twice-yearly injections are easier to maintain than a daily pill and showed dramatically better practical outcomes in these trials, continuing to randomize participants to the less convenient option raised ethical concerns. A 52-week post-vaccination follow-up period was used to screen and confirm HIV status changes.

Why lenacapavir works: the science behind the protection

Lenacapavir targets a structural protein on the exterior of the HIV capsid — a component that is highly conserved across viral strains. By binding to this capsid protein, the drug sabotages the virus’s ability to assemble and disassemble its protective shell at several points in its life cycle.

• This disruption prevents HIV from completing vital steps needed to replicate and infect new cells.
• Because the target is a highly conserved protein, the drug retains activity even as the virus mutates into different variants.
• Delivered subcutaneously, the formulation maintains protective drug levels for months, allowing a twice-yearly dosing schedule.

Practical benefits: adherence, stigma reduction, and programmatic advantages

The difference between an effective pill and an effective program often comes down to real-world adherence. Daily regimens require consistent behavior over months and years; missed doses can lower protection. The six-month injection model addresses several practical barriers:

• Improved adherence: Two clinic visits per year greatly reduce the chance of missed doses compared with daily pills.
• Reduced stigma: People no longer need to carry or be seen taking a pill that signals HIV-related risk, a benefit in places where stigma or criminalization persists.
• Programmatic ease: Health services can schedule injections alongside other routine care, simplifying delivery at scale.

Regulatory status, recognition, and cost commitments

Lenacapavir has received high-profile scientific recognition and regulatory approvals. Science magazine named it Breakthrough of the Year (2024), and the U.S. Food and Drug Administration approved the drug for human use under the brand name Yeztugo.

Developing a new antiviral from discovery through late-stage trials, regulatory review, and manufacturing typically costs well over a billion dollars. The drug’s developer, Gilead Sciences, has pledged specific access measures for lower-income regions:

• Commitment to provide lenacapavir at cost in selected low-income settings.
• Licensing agreements with generic manufacturers to produce affordable versions, with a target price of roughly $40 per year in about 120 low- and middle-income countries starting in 2027.

Implications for global HIV prevention strategies

These trial outcomes suggest that long-acting injectable PrEP could become a central pillar in efforts to curb new HIV infections, especially in regions with persistent high incidence. Health systems, funders, and community programs will need to consider logistics for delivering twice-yearly injections, supply-chain needs for widespread rollout, and how to integrate this option alongside existing prevention tools.

As national programs evaluate whether to adopt lenacapavir-based PrEP, questions around manufacturing scale-up, cost-effectiveness analyses, and targeted outreach to populations at highest risk will shape the speed and scale of implementation.

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Michael Thompson

Michael Thompson is an experienced journalist covering U.S. and global news. With ten years on the front lines, he breaks down political and economic stories that matter. His precise writing and keen attention to detail help you grasp the real‑world impact of every event.