From promise to programs—How to ensure PrEP science is translated into global impact

.FIRST PERSON. This is part of a series of personal stories and commentaries launched on World AIDS Day 2025

A transformative chapter for global HIV prevention started 17 months ago when Gilead Sciences announced that a phase 3 trial (PURPOSE 1) of twice-yearly injectable lenacapavir (LEN) showed 100% efficacy against HIV among cisgender women. A few months later, a sibling trial among cisgender men and gender diverse individuals also showed very high efficacy. Then came swift guidance and recommendation from the World Health Organization (WHO) and regulatory approvals in the U.S., Europe, South Africa and Zambia. The latest news is an agreement between Gilead Sciences, the product developer, and the two largest global HIV programs—the Global Fund and the U.S. State Department through PEPFAR. Together, they will deliver LEN to two million people over three years to ten early introductory countries in Africa along with the Philippines and Ukraine. These are the first crucial steps towards increasing global access to long-acting PrEP, but critical unanswered questions remain. 

LEN represents groundbreaking innovation: a long-acting agent that could protect an individual with injections only twice a year (after an initial dose of four pills). On a global level, this option could be terrific for people who struggle with taking a daily pill for a variety of reasons such as HIV stigma, unstable housing, and limited access to clinics—factors that reflect social determinants of health. Importantly, LEN should not replace existing PrEP options currently on the market. Different people have different needs, preferences and bodies, which change at different stages of life. Diverse choices respond to this range of needs. 

The real promise of lenacapavir goes beyond the drug itself, by offering more choice, more flexibility and a better chance that everyone can find an HIV prevention option that fits their life. The real test now is whether the field can turn this scientific breakthrough into equitable access. 

In a year when the U.S. government has challenged science and research at its core, twice-yearly LEN has been prominently featured in plans across federal agencies. The State Department’s new America First Global Health Strategy retains HIV as a core priority and ties foreign assistance to time-bound, results-oriented agreements that emphasize innovative essential medicines and health workers. This framing of global health is more digestible to the Trump administration, cast as a “win-win” for U.S. security and partner-country health systems. 

At the same time, the agreement by the Global Fund, Gilead and State Department will bring LEN to early adopter countries with a high burden of HIV, deliver it faster, and shape the market rapidly for uptake. This accelerated introduction paves the way for generics to enter the market. Gilead provided six voluntary licenses, and two of them have been supported with Unitaid and Gates Foundation investments. Market access is expected in 2027, and the price is expected to drop considerably. 

In addition, the National Institutes of Health (NIH) has put a heightened focus on HIV implementation science to close a widening gap between discovery and practice. NIH is funding studies and supporting community-led models that will show how to deliver twice-yearly LEN in real clinics without deepening inequities. These are bold commitments on paper, but—as the saying goes—the devil is in the details, and real impact will depend on implementing these ambitious plans with the community, not without them or around them.

Now, time for the reality check.

Several factors could stall LEN uptake as plans move from strategies and agreements on paper to real-world global rollout. Fundamental questions remain about the State Department’s ambitious new plan: prevention, including PrEP, is not explicitly written into goals, indicators or budgets, and the lack of PEPFAR data since 2024 does not bode well for tracking progress on access and uptake. The agreement between the Global Fund, Gilead and the State Department currently raise more questions than confidence; the deal lacks basic transparency, omitting crucial details such as price per dose, even though it’s rumored to be about $100 per person per year, which is still 2.5 times the price of generic oral PrEP.

The NIH agenda for implementation science for LEN also has some critical gaps: strong partnerships with global research institutions will be essential to understand how to roll out LEN in diverse settings, yet this will be difficult to achieve when international research grants have been paused or terminated. Domestic-focused implementation studies alone will not answer critical and complex questions, but a multi-country effort can. 

These gaps are compounded by a lack of meaningful engagement with HIV communities—including researchers and advocates—who should be core partners in shaping, reviewing, and implementing an agenda for rolling out LEN. Fulfilling the promise of LEN for PrEP will depend on building a new architecture of solidarity, funding and accountability among all these stakeholders. One that is strong enough to make LEN real for the people most at risk—even after the dismantling of USAID and the curtailment of PEPFAR.

In addition, it’s also essential to ensure a robust pipeline of HIV prevention technology against HIV, a constantly changing virus, in order to achieve epidemic control. Any shift toward implementation science at NIH must be matched by sustained investment in basic science, vaccine and cure research, and other prevention tools. LEN is a powerful new option, but it is not a silver bullet or miracle drug—and it cannot replace the need for a diverse prevention pipeline. Another long-acting option, Merck’s MK-8527 monthly oral PrEP pill now entering phase 3 trials, is one example of the innovation that must continue.

So, where to from here? Program freezes, staffing cuts and mixed messages from donors and governments have already slowed HIV prevention globally. When prevention isn’t explicitly named in national plans, when targets aren’t set, and when data on PrEP use and coverage aren’t routinely collected and shared, access to PrEP is lost to competing priorities. Clear, public commitments from funders and governments that LEN will be part of the core HIV prevention package is essential. To achieve impact against the epidemic, PrEP in all its forms cannot be a boutique option, reserved for a privileged few. It must be a standard option in programs that are robustly funded, staffed, and measured to deliver.

The priorities below outline what it will take to ensure this best shot at HIV prevention is seized and not squandered: 

1. Follow the money: Sustain and maximize funding for PEPFAR, NIH, and the Global Fund.

• Prioritize a strong Global Fund replenishment.

• Ensure the administration actually spends all Congressionally appropriated funds at State/PEPFAR and NIH. 

2. Build a sustainable market for LEN and beyond: Create a market where multiple generic manufacturers can compete for large volumes, driving prices down and impact up.

3. Invest in demand generation: Fund community-led campaigns, education, and outreach—LEN won’t scale if people don’t know about it or can’t trust it.

4. Put communities at the center, not on the sidelines: Require that community leaders, especially those from the most affected populations, have real decision-making power—not just “consultation”—in planning, policy development, program design and funding decisions related to LEN and broader HIV prevention efforts.

5. Make data transparent and predictable: Commit to regular, timely data releases so countries can track prevention progress and make informed decisions about LEN scale-up.

6. Be creative with partnerships: Encourage NIH and PEPFAR to jointly support implementation research on LEN, linking science, service delivery and community leadership across geographies and populations.

7. Frame LEN as part of a combo of prevention, not a silver bullet: There are no miracle drugs in the HIV response. Deliver LEN alongside all PrEP options, condoms, VMMC and treatment as prevention, and continue to invest in developing the next generation of HIV prevention options that are still needed.

Bottom line: scientific publications and ambitious plans don’t protect people—unfettered access to PrEP pills, rings and shots does. If the U.S. wants LEN to matter beyond the press release, it must move fast, reach far, and center the communities most at risk. Speed + scale + equity = impact—or this LEN moment will be remembered as a missed opportunity, not a turning point.