The only thing standing between humanity and the end of HIV

How often, on average, do you forget to take your daily meds?

For me, it’s about twice a week. And that’s for something as low stakes as a vitamin D supplement; it’s not the end of the world if I’m a little deficient. But when it comes to HIV prevention, missing a dose of your prescribed daily prevention pills could mean the difference between protection and new infection.

A new drug called lenacapavir might entirely change the game, though.

Right now, our most widely used tool to stave off HIV — which killed an estimated 630,000 people last year — is through prevention pills, called pre-exposure prophylaxis. PrEP works extremely well and has prevented millions of HIV infections in the 13 years it’s been around. But the catch is that it needs to be taken every single day. In much of the Global South, having consistent access to it remains a big hurdle, on top of issues with adherence and stigma.

That’s the reason why, by 2023, only about 6 million people worldwide were on PrEP, a fraction of the tens of millions who could benefit. Each year, another 1.3 million people still acquire HIV.

But a discreet shot taken just twice a year, like the newly approved lenacapavir, takes forgetfulness — and some stigma — out of the equation. For a field where breakthroughs have been rare, lenacapavir has almost vaccine-like efficacy (even though it’s not one). In clinical trials, the drug showed 100 percent protection in women and approximately 96 percent in men, transgender and nonbinary people. Those are the kind of numbers policymakers can’t ignore.

The US Food and Drug Administration approved it in June, the World Health Organization endorsed it in July, and the European Union followed in August. And the Trump administration — which grounded its live-saving global health work to a complete stop eight months ago — has recently made lenacapavir the center of its “America First” global health strategy. The administration plans to roll out the drug in about a dozen low-income countries by early 2026.

That’s all remarkable news. Low-income countries typically have had to wait decades, if not more, before newer, better drugs trickled down. This time, at least in theory, access could come almost simultaneously.

But whether lenacapavir actually makes a dent in the HIV epidemic will depend less on science than on politics.

Four decades ago, an HIV infection was a near-death sentence. But since then, we’ve marched toward progress — making better drugs with simpler regimens and widening access.

But even after all that work, we still don’t have a cure or a true vaccine. That’s why an innovation like lenacapavir feels notable.

For years, HIV drugs targeted the virus’s enzymes, and it wasn’t obvious that targeting anything else would work. Then in the 1990s, researchers backed by the National Institutes of Health began studying how the virus builds its cone-shaped shell, called the capsid. Most scientists dismissed it as “undruggable” — a smooth protein structure with no obvious place for a medicine to stick.

But a small band of virologists thought differently. They spent years hunting for a molecule that could jam the capsid’s formation. After countless dead ends, that hunch paid off: The work led to lenacapavir, the first drug to successfully attack the virus’s shell and block multiple steps in its life cycle.

In a landmark clinical trial that began in 2021 and enrolled more than 2,000 teen girls and young women from South Africa and Uganda, no one who received lenacapavir contracted HIV. The effect was so striking that, in June 2024, an independent safety board told researchers to end the trial’s blinded phase early — continuing would’ve meant withholding an obviously effective drug from some participants.

“It would’ve been unethical not to,” said Linda-Gail Bekker, an infectious disease physician at the University of Cape Town and one of the trial’s lead investigators.

Those numbers are really impressive, but lenacapavir’s efficacy as an injectable is another plus. In much of sub-Saharan Africa, where HIV burden is among the heaviest, injectable contraception is already the most widely used form of birth control. For many women, injections are more discreet and practical than taking a daily pill. “It’s a very recognized concept…injections are a very attractive option,” Bekker said. That familiarity could be the difference between a prevention tool that works in theory and one people actually use.

As lenacapavir emerged from late-stage trials, with results showing near-perfect protection, the world took notice. In 2024, the editors of Science, the prestigious scientific journal, named lenacapavir their breakthrough of the year. “This drug is extraordinary — the closest thing to a vaccine that we have,” said Dr. Megan Ranney, the dean of the Yale School of Public Health and one of the Science editors.

A twice-yearly shot that can nearly eliminate new infections should be the stuff of celebration. Lenacapavir could mark the beginning of the end of HIV.

But as always in public health, the science is only half the story.

A breakthrough only matters if it gets off the shelf and reaches the people who need it most. And in much of the world, that depends on policymakers.

Since 2003, the US President’s Emergency Plan for AIDS Relief, or PEPFAR, has been an essential, global lever for HIV treatment access. PEPFAR is a George W. Bush-era program that has delivered lifesaving HIV treatment to poor countries and has helped save more than 25 million lives over its 22-year history. The program is funded by the US Congress, which renews its authority and budget — both of which can get caught up in politics.

When President Donald Trump returned to office in January, he ordered a broad freeze on US foreign aid, throwing PEPFAR into limbo. Grants were halted, drug shipments stalled and USAID — the program’s main implementer — was dismantled almost overnight, stoking fears that the world’s most successful HIV program was about to be killed off.

Then last month, the administration announced its plans to revive PEPFAR to deliver the breakthrough drug lenacapavir. (But right now, it’s unclear how the ongoing government shutdown will affect PEPFAR funding.)

The administration says it will prioritize delivering lenacapavir to pregnant and breastfeeding people in eight to 12 yet-to-be-announced countries, as part of Trump’s push to end mother-to-child transmission of HIV by the end of his term. On paper, that’s a tidy goal — two injections can protect both mother and baby through pregnancy and nursing — but advocates say that choice isn’t rooted in science.

In sub-Saharan Africa, young women, broadly, account for the majority of new infections, and elsewhere, it’s gay and bisexual men, trans people, sex workers, and people who use drugs — those who were disproportionately infected and died in the early decades of the HIV epidemic. Now, channeling the new drug only through maternal health programs risks leaving those communities out yet again.

“Prioritizing pregnant and breastfeeding people is ideological, not scientific,” said Asia Russell of HealthGAP, a New York City-based AIDS advocacy organization. “They’re a very, very small fraction of those at risk.” In sub-Saharan Africa, pregnant and breastfeeding people face real risk — a few out of every hundred contract HIV each year — but they’re still a small slice of a larger epidemic that’s largely driven by young women and queer men.

State Department official Jeremy Lewin also made their philosophy clear during the administration’s announcement. “There are no NGOs involved in this — none of those sort of beltway bandits here,” he said, referring to the aid groups that have traditionally implemented US-funded HIV programs. (It’s a loaded term and a misleading one, given that oversight bodies haven’t uncovered corruption at scale.) “It’s going to be the countries [who are] responsible for distributing it through their national healthcare systems.”

That might sound efficient in Washington, but it’s more complicated on the ground.

That’s because HIV isn’t like cholera or the flu — something you can beat with a one-size-fits-all campaign. It affects some groups more than others and carries deep stigma, because it’s tied to sex, sexuality, and drug use, all of which are moralized in many societies. And in many countries, the state is the very institution that enforces, even criminalizes, that stigma.

Bekker, who runs an HIV research center in South Africa, said that even in places without formal bans, public clinics can feel hostile to sexual and gender minorities. “The result,” she said, “is that people just don’t show up.”

PEPFAR’s own history shows that prevention works best when community-led groups such as LGBTQ+ clinics or drop-in centers are included in the response. Those are the spaces that reach groups left out by official systems. Jirair Ratevosian, a former senior PEPFAR adviser, said ending infant infections is crucial, but so is supporting community- and faith-based clinics “where people actually feel safe.”

Besides the Trump administration (and all its political theater), there’s one more key player: Gilead Sciences, the California-based company that developed lenacapavir.

In September, Gilead made two big promises. First, it agreed to sell lenacapavir to PEPFAR at “no profit,” although it’s unclear what that actually means. Second — and more importantly — it signed licensing deals with six generic manufacturers, sharing its technology so those companies can start preparing to make cheaper versions.

Typically, drug companies fiercely guard new medicines under patents for 20 years, during which time they alone can make and sell the drugs — and only countries that can afford the list price get access. Once those patents expire, generics can enter the market and drive costs down.

By making these licensing deals, Gilead is trying to shorten that wait time so, if all goes to plan, poorer countries could get lenacapavir in just a few years instead of decades later.

The licensing deal allows generics to be sold in 120 low- and lower-middle-income countries, covering most of the world’s poorest nations. Once those versions hit the market, they’ll cost a fraction of Gilead’s price tag — which in the US is $28,128 a year per patient, though few people pay that sticker price.

But the deal leaves out many upper-middle-income countries such as Brazil or Argentina, where infections have been rising. Those nations fall into a gray zone — too rich for cheap generics, too poor to afford Gilead’s prices.

For Gilead, a for-profit company, sharing its drug formula with generic makers might sound generous, but it’s not as straightforward as it looks. The licenses “carve the world into low-value markets where generics can operate [where Gilead won’t be making money anyway], and profitable ones where Gilead keeps its grip,” said Tahir Amin, an intellectual-property lawyer and co-founder of Initiative for Medicines, Access, and Knowledge, a nonprofit that advocates for patent reform.

Meanwhile, major philanthropists — the Gates Foundation, Unitaid, Clinton Health Access Initiative, and Wits RHI — are doing their part to help generics reach the market faster. They’re backing two Indian generic manufacturers with funding and technical support to help scale production so that low-cost versions of the drug are available by 2027. If that works, it would cost just $40 per person per year — roughly what daily oral PrEP costs today.

If that happens — that is if we’re able to make cheaper generics faster, roll them out equitably, and deliver them where people feel safe — lenacapavir could make a real dent in the HIV epidemic.

Breakthrough science doesn’t guarantee a breakthrough in public health. That will depend on the choices made now.