It started with a bunch of curious biochemists in a University of Utah lab trying to figure out how the HIV particle is put together. This research, led by Wesley Sundquist, achieved yet another milestone this week when the U.S. Food and Drug Administration approved an antiviral drug, based on Sundquist’s findings, for HIV prevention.

In clinical trials, the first-in-class drug, known as lenacapavir, has been shown to greatly reduce the sexual transmission of HIV with just two injections a year, a breakthrough that is hoped to beat the AIDS epidemic that has killed millions around the world since the 1980s.

Building on discoveries made in Sundquist’s Utah lab, California-based Gilead Sciences developed lenacapavir and is marketing it under the brand name Yeztugo. The FDA decision makes the drug available in the United States, which sees about 31,000 new HIV infections a year.

“This is a historic day in the decades-long fight against HIV. Yeztugo is one of the most important scientific breakthroughs of our time and offers a very real opportunity to help end the HIV epidemic,” said Gilead CEO and Chairman Daniel O’Day in a news release. “This is a medicine that only needs to be given twice a year and has shown remarkable outcomes in clinical studies, which means it could transform HIV prevention.”

But the story of lenacapavir started decades ago with basic, curiosity-driven research in Sundquist’s lab. The lab wasn’t specifically aiming to discover new therapies—rather, they were simply trying to understand HIV’s molecular structure, according to Sundquist, who is the Samuels Distinguished Professor and chair of the U’s Department of Biochemistry in the Spencer Fox Eccles School of Medicine. 

“When we started the work, we were mostly driven by curiosity,” he said in a Vitae Vignettes video produced by U Health. “The two things that motivated us most were trying to understand how the virus makes a conical capsid, that’s the structure in the center of the virus that is responsible for replication. And then how does the virus use that conical capsid to do replication?”

 

They found a critical component of the virus that is extremely sensitive to change: a prime target for drug development. Gilead used these insights to develop a drug that blocks the functions of the HIV capsid, hampering the virus’s ability to multiply in cells.

The FDA approval was based on Phase 3 trial data that showed 99.9% of the 2,179 participants receiving the twice-a-year injections remained HIV negative.

“It’s more potent than any drug available, but more importantly, it’s very long-lasting. So what the Phase 3 clinical trials show is that it completely protects people from transmission for six months,” Sundquist said. “There are still 1.3 million new infections worldwide, and this could really change that trajectory. Of course, the rollout has to be funded and be successful, but right now there’s no reason to think this won’t have a major impact.”

About 40 million people live with HIV, resulting in about  600,000 deaths a year, according to the World Health Organization.

Also this week, Sundquist was awarded the 2025 Warren Alpert Prize from Harvard University for his discoveries that led to the new drug. Also honored were Gilead executives Tomas Cihlar and John O. Link. Earlier this year, the discovery earned Sundquist and Cihlar a spot on TIME’s list of the world’s 100 most influential people of 2025 and was hailed by Science magazine as the 2024 Breakthrough of the Year.

Yet when they were conducting their experiments, Sundquist and his lab colleagues had no idea the research could someday crack the scourge of AIDS.

“We view ourselves as sort of the feedstock for new ways of approaching medicine,” Sundquist said. “We’re driven by curiosity to discover things that we don’t understand. And I think that’s not so different from other kinds of adventurers. The same thing that drives people to discover or climb mountains, I think, drives us to discover how a molecular machine works.”

• Sophia Friesen Manager, Science Communications, University of Utah Health
  ‭(510) 495-7528‬ sophia.friesen@hsc.utah.edu