Last Updated on July 18, 2025 by Royce Pierpont

A revolutionary breakthrough in HIV prevention has sparked hope for millions worldwide, as the World Health Organization (WHO) endorses a twice-yearly injectable drug, lenacapavir, as a powerful tool to curb new HIV infections. Unveiled at the 13th International AIDS Society Conference (IAS 2025) in Kigali, Rwanda, this long-acting pre-exposure prophylaxis (PrEP) option could redefine global efforts to combat HIV, particularly for high-risk communities. However, experts warn that challenges in funding, accessibility, and stigma could hinder its transformative potential.

A New Era in HIV Prevention

Lenacapavir, marketed as Yeztugo for prevention and Sunlenca for treatment, is a capsid inhibitor developed by Gilead Sciences. Unlike traditional PrEP options, such as daily oral pills like Truvada or bimonthly injections like Apretude, lenacapavir requires only two subcutaneous injections per year. This innovation addresses one of the biggest barriers to HIV prevention: adherence. For many, taking a daily pill or scheduling frequent clinic visits is a logistical or social challenge, often compounded by stigma or limited healthcare access.

Clinical trials, notably the PURPOSE 1 and PURPOSE 2 studies, have demonstrated lenacapavir’s remarkable efficacy. In PURPOSE 1, conducted among over 5,300 cisgender women in South Africa and Uganda, no participants receiving lenacapavir contracted HIV, achieving 100% efficacy compared to a background HIV incidence of 2.41 per 100 person-years. PURPOSE 2, involving over 3,200 cisgender men, transgender women, transgender men, and gender-nonbinary individuals, reported only two infections among 2,179 participants, translating to a 96% reduction in HIV risk. These results, published in The New England Journal of Medicine in November 2024, led Science magazine to name lenacapavir the “Breakthrough of the Year” in 2024.

“Lenacapavir is a game-changer,” said Dr. Meg Doherty, director of WHO’s Department of Global HIV, Hepatitis, and Sexually Transmitted Infections Programmes. “Its long-acting nature means people can protect themselves discreetly with just two clinic visits a year, overcoming barriers like stigma and pill fatigue.”

Why Lenacapavir Matters

HIV remains a global health crisis, with approximately 40.8 million people living with the virus in 2024, according to UNAIDS. Despite a 39% reduction in new infections since 2010, 1.3 million people acquired HIV last year, and 630,000 died from AIDS-related causes. Key populations—sex workers, men who have sex with men, transgender individuals, people who inject drugs, and incarcerated individuals—face disproportionate risks, particularly in regions like sub-Saharan Africa, which accounts for two-thirds of global HIV cases.

Lenacapavir’s twice-yearly dosing schedule offers a practical solution for these groups. “For individuals who struggle with daily regimens or face stigma storing oral PrEP at home, lenacapavir is a lifeline,” said Dr. Edward Liu, chief of infectious diseases at Hackensack Meridian Jersey Shore University Medical Center. “It’s a set-it-and-forget-it approach that could save lives.”

The drug’s mechanism is unique. As a capsid inhibitor, lenacapavir targets the HIV virus’s structural protein, disrupting its ability to replicate. This dual action—preventing viral entry into cells and inhibiting the formation of mature virus particles—makes it highly effective and less likely to face resistance, as it has not been widely used.

Global Endorsement and Simplified Testing

WHO’s recommendation, announced on July 14, 2025, emphasizes lenacapavir’s role in a comprehensive HIV prevention strategy. The organization also advocated for simplified HIV testing using rapid diagnostic tests, such as at-home kits, to support the rollout of long-acting PrEP. This approach eliminates costly and complex procedures, enabling community-based delivery through pharmacies, clinics, and telehealth platforms.

“By combining lenacapavir with accessible testing, we’re removing barriers and empowering communities to take control of their health,” said Dr. Tedros Adhanom Ghebreyesus, WHO Director-General. “While a vaccine remains elusive, this is the closest we’ve come to a preventive tool with vaccine-like impact.”

The endorsement aligns with global goals to end the HIV epidemic by 2030, as set by UNAIDS. However, experts caution that success hinges on rapid implementation and equitable access.

Challenges on the Horizon

Despite its promise, lenacapavir’s rollout faces significant hurdles. The drug’s high cost—approximately $28,218 annually in the U.S.—raises concerns about affordability, particularly in low- and middle-income countries where HIV prevalence is highest. Gilead Sciences has pledged to supply lenacapavir at no profit to the Global Fund to Fight AIDS, Tuberculosis, and Malaria, targeting two million people in 120 resource-limited countries. Additionally, the company has granted voluntary licenses to six generic manufacturers to produce affordable versions, though scaling up production could take two to three years.

Funding cuts further complicate the picture. The Trump administration’s recent reductions to the President’s Emergency Plan for AIDS Relief (PEPFAR) and the U.S. Agency for International Development (USAID) have slashed resources for global HIV prevention. PEPFAR, which has historically funded 80% of HIV programs in low-income countries, faces uncertainty, threatening the infrastructure needed to distribute lenacapavir. In the U.S., proposed Medicaid cuts could limit access for high-risk populations, despite states with expanded Medicaid showing 33% higher PrEP uptake.

“Lenacapavir is a scientific triumph, but without funding and infrastructure, it’s like building the best plane and tearing up the runways,” said Kevin Frost, CEO of amfAR, the Foundation for AIDS Research.

Stigma remains another barrier. In some communities, particularly in sub-Saharan Africa, individuals avoid PrEP due to fears of being perceived as HIV-positive or engaging in high-risk behavior. Lenacapavir’s discreet administration could mitigate this, but public education campaigns are essential to normalize its use.

A Path to 2030

Despite these challenges, optimism abounds. The FDA approved lenacapavir for HIV prevention in June 2025, making the U.S. the first country to authorize its use as PrEP. Other regulatory bodies are reviewing the drug, with approvals expected in the coming months.

Experts like Dr. Monica Gandhi of the University of California, San Francisco, highlight lenacapavir’s potential to serve marginalized groups. “In our clinic, we’ve seen higher retention rates with long-acting PrEP like cabotegravir among people facing housing insecurity or substance use challenges. Lenacapavir’s six-month duration could amplify this impact,” she said.

To maximize lenacapavir’s reach, WHO is collaborating with partners like the Global Fund and UNAIDS to integrate it into national HIV programs. Community-based delivery models, such as mobile clinics and telehealth, are being explored to ensure access in remote areas.

Looking Ahead

Lenacapavir’s approval marks a pivotal moment in the fight against HIV. Its near-perfect efficacy, minimal side effects (primarily mild injection-site reactions), and long-acting nature position it as a cornerstone of global prevention efforts. However, its success depends on overcoming systemic barriers.

“We’re at a crossroads,” said Mitchell Warren, executive director of the AIDS Vaccine Advocacy Coalition. “Lenacapavir could help us meet the 2030 target to end HIV, but only if we act swiftly to ensure access for those who need it most.”

As the world grapples with funding uncertainties and logistical challenges, lenacapavir offers a beacon of hope. By simplifying prevention and empowering communities, this twice-yearly shot could bring us closer to a world without AIDS—if we can seize this moment.