Progress against H.I.V. marks one of the greatest accomplishments of biomedical research in history. Four decades ago, an H.I.V. infection meant an early, painful death. Scientists went on to develop powerful antiretroviral treatments that staved off AIDS and curbed H.I.V.’s spread. Yet, in 2023, 1.3 million people around the world became infected—more than thirty-five hundred per day, nearly a hundred and fifty every hour. Treatments only work if you take them, and many people do not know that they have H.I.V. Even for those who are aware of their status and can access the drugs, the virus integrates with human chromosomes and never clears, meaning that people living with H.I.V. must take medication for the rest of their lives. In 2023, almost forty million people were living with H.I.V., and six hundred and thirty thousand died from AIDS.
Then, in June, 2024, Moupali Das, the head of H.I.V. prevention for the pharmaceutical company Gilead Sciences, received an e-mail about lenacapavir, a drug being tested by the company to prevent the spread of H.I.V. The message authorized Das to see the results from an ongoing clinical trial in South Africa and Uganda. When she reviewed the data, at her company’s sprawling campus in Foster City, California, she had to move closer to her computer’s screen to confirm that she was reading the numbers correctly. She was dumbstruck: What she thought was a zero really was a zero. More than two thousand teen girls and young women had been injected with the drug, which stays in the body for an astonishing six months. In the first year of the trial, each received two shots, and none of them became infected with H.I.V. “It was phenomenal,” Das told me. “We thought it was going to work, but none of us thought it was going to be one hundred per cent.” Three months later, the drug demonstrated ninety-six-per-cent efficacy in a similar trial that had enrolled more than three thousand men, transgender men and women, and nonbinary people who have sex with men.
For nearly twelve years, Gilead had been selling a pill named Truvada as a preventive treatment called pre-exposure prophylaxis, or PrEP. The drug worked remarkably well in clinical trials, but many healthy people had difficulty taking a daily pill, and others faced stigma and discrimination from sexual partners. Another company, ViiV Healthcare, brought a PrEP injection to market in 2021, but it only lasts two months, and remains little used. If two shots a year offered the same protection, Das knew, it could revolutionize H.I.V. prevention. On June 18th, the F.D.A. approved lenacapavir for PrEP. A stunning new era is upon us. But, as world leaders dismantle global health programs and cut back foreign aid, will this extraordinary new technology be able to change the world?
When scientists first started talking about using drugs to prevent the spread of H.I.V., few expected that Gilead would be the company to develop them. In the early nineteen-nineties, the top anti-H.I.V. drugs on the market had at most a modest impact: they were reserved for people with severely damaged immune systems and, at best, only extended life by a few years. Side effects included diarrhea, nausea, headaches, and anemia. As the death toll approached a million per year, big pharmaceutical companies competed to create better treatments. Gilead, a small corporation that had a few hundred employees, was an underdog in the race. But it licensed a promising compound, tenofovir, from academics in Europe.
During that bleak era, Che-Chung Tsai, a researcher at the University of Washington, contacted several companies, seeking experimental drugs for use in an animal study. Gilead sent him an early form of tenofovir, which produced remarkable results. When a group of monkeys were given the compound before being exposed to H.I.V.’s simian cousin, S.I.V., not a single one was infected. What’s more, the drug had no significant adverse effects.
H.I.V. is made up of single-stranded RNA rather than double-stranded DNA. To infect its host, it enters white blood cells, uses a viral enzyme called reverse transcriptase to convert its RNA into DNA, and hijacks the cell’s machinery to make more copies of itself. Tenofovir works by crippling this enzyme. In a person with H.I.V., tenofovir prevents the virus from making new copies of itself.
Yet tenofovir also showed promise for people who did not have H.I.V. The monkey study found that, when a healthy animal received tenofovir, the virus was like a bullet that fell to the ground before striking its target: the RNA virus couldn’t convert itself into DNA, so it couldn’t splice itself into the DNA of the host.
Despite the drug’s potential as PrEP, Gilead made little effort to support the research: preventive drugs had unique risks. In uninfected people, it’s harder to prove that the benefits of a drug will outweigh potential risks, raising liability concerns. Some feared that widespread use of PrEP might breed resistant strains of the virus itself. And although millions of H.I.V.-positive people were desperate for effective drugs, it wasn’t clear that people at the highest risk of infection—gay men, sex workers, people who injected drugs, sexually active heterosexuals in sub-Saharan African countries—would want PrEP or be able to access it. And so Gilead focussed instead on the lucrative and stable market of H.I.V. treatments. In 2001, tenofovir won F.D.A. approval for treating H.I.V. infections. The next year, the drug accounted for about half of the company’s sales.
Gilead’s disinterest in PrEP deeply frustrated academic researchers. In 2003, to confirm that tenofovir would work as well in humans as it had in monkeys, researchers announced plans to recruit sex workers for a clinical trial in Cambodia. Gilead kept itself at a distance from the study; the National Institutes of Health (N.I.H.) and the Bill and Melinda Gates Foundation offered to fund the research. But some AIDS activists were enraged by the trial’s design. They argued that researchers were introducing risk of infection to people in a country with limited treatment resources. In July, 2004, at an international AIDS conference in Bangkok, a group descended on a Gilead Sciences booth and plastered it with posters: “Sex Workers Infected by Gilead,” “Tenofovir Makes Me Vomit,” and “Gilead Prefers us HIV+.” As news cameras from around the world gathered around the scene, the activists covered signs in fake blood. Soon after, the trials in Cambodia were abandoned. Though Gilead provided academic researchers use of the compound for PrEP studies, they declined to pursue further preventive testing on their own.
A month after the Bangkok conference, the F.D.A. approved a new H.I.V. treatment, produced by Gilead, called Truvada, which combined tenofovir with a second drug. At the time, regimens typically required three drugs, several times a day. The new compound, a pill taken once a day, could be combined with just one other drug, simplifying treatment. By 2006, Truvada was the best-selling anti-H.I.V. drug on the market.
Flush with cash, Gilead launched an ambitious project to create a new drug targeting an H.I.V. protein called capsid. Many scientists saw Gilead’s project as folly: viral proteins have no obvious weaknesses, making them far less druggable than viral enzymes. Researchers had long thought that capsid proteins—which link together to form a protective shell, known as a cone, around the RNA—simply fell apart after infecting a cell. But a series of stunning discoveries found that the capsid cone not only survives infection but plays a far more complex role in the production of new viruses. With this insight, Gilead tested thousands of compounds, leading to the discovery, in 2012, of what would become lenacapavir.
That same year, Gilead finally sought F.D.A. approval for Truvada as PrEP. It was approved in July. A drug for prevention was a major turning point, yet it was met with ambivalence by some of the communities most affected by the virus. Even the primary market for the drug, gay men in the United States, had strong reservations about taking the pills to protect themselves. Critics feared it created incentives for uninfected men to abandon condoms and increase their number of sexual partners, undermining years of hard-won progress in prevention. Worries ran so high that some gay men for a time slagged people who used PrEP as “Truvada whores.”
Truvada PrEP steadily gained popularity, and as it grew cheaper it became more widespread in poorer countries. In March, 2019, Gilead reported that lenacapavir had performed well in early human studies. Gilead’s risky investment was showing signs of paying off—and this time, the company was eager to get ahead of its critics.
In December, 2019, Das flew to Kigali, Rwanda, to meet with community advocates and public-health leaders from across the continent. Lenacapavir was going to be tested as a prevention tool; the company wanted input on the design of the trials. How could the company’s researchers avoid the community opposition that had dogged the Cambodia trial? Should they include pregnant people? What about adolescents as young as sixteen? Earlier research had been roundly criticized for excluding both groups, as well as for cutting out trans people and anyone taking hormones. Yvette Raphael, a human-rights activist who chairs the African Women Prevention Community Accountability Board, left the meeting reluctantly impressed. “It was tough because, obviously, they are a pharmaceutical company, and we are advocates,” Raphael said recently. “We’d like to see more transparency from them—but they really have tried.”
The company has also made efforts to increase access to preventive lenacapavir. After a drug is approved, years often pass before generic manufacturers are allowed to sell it at a discount. But in October, 2024, Gilead—still months away from even seeking F.D.A. approval—announced that it had cut a deal with six generic manufacturers to provide low-cost versions of lenacapavir PrEP to a hundred and twenty poorer countries. While those producers are getting up and running, a process that may take an estimated two years, Gilead will sell lenacapavir to the same countries at cost. “They learned from their mistakes,” Mitchell Warren, the executive director of AVAC, an advocacy group for PrEP and other H.I.V.-prevention interventions, told me. “At least conceptually, this is one of the most transformational moments in H.I.V. prevention ever.”
Two months later, near the end of the Biden Administration, a major partnership set out to make injectable preventive lenacapavir available to at least two million people during its first three years on the market. It would bring together the President’s Emergency Plan for AIDS Relief, or PEPFAR; the deep-pocketed Global Fund to Fight AIDS, Tuberculosis, and Malaria; the Gates Foundation; and the Children’s Investment Fund Foundation.
Then came another seismic shift in the H.I.V./AIDS world. On the day President Donald Trump took office, his Administration began dismantling PEPFAR, which has spent more than a hundred and twenty billion dollars in more than fifty countries over the past two decades—not only to support the treatment of twenty million people but also to purchase and deliver more than ninety per cent of PrEP drugs used globally. A State Department memo in February stated that, during this pause of U.S. Foreign Assistance or until further notice, PEPFAR could only support PrEP for pregnant and breast-feeding women.
The fate of the rollout of lenacapavir PrEP remains murky. Although neither the Gates Foundation nor the Global Fund has committed to honoring their original pledge, both have indicated that they still plan to support “equitable access” to lenacapavir PrEP. (What this means, in practice, is difficult to say.) The White House, earlier this month, released its Congressional Budget Justification for fiscal year 2026 that calls for continued support for PEPFAR, with a budget cut of thirty per cent and a desire to speed its elimination; it specifically mentions funding for “high cost-efficiency biomedical tools, such as a twice-a-year HIV prevention injection.”
Injectable lenacapavir, despite its clear benefits, faces several other financial, political, and cultural challenges that have dogged PrEP from the outset. Will insurance companies reimburse for it in full? How aggressively will health officials promote its use? Will communities embrace it? “We have not seen evidence of the bigger resources being devoted and the political will to do what needs to be done to get any of these PrEP options into the populations that need it the most,” says Raphael Landovitz, an H.I.V./AIDS researcher at the University of California, Los Angeles, who has helped run other PrEP studies. “Everything we have seen is incremental. And so I fear that this is going to be yet another incremental improvement.”
