SALT LAKE CITY — Roughly 630,000 people died of HIV-related illnesses worldwide in 2023, according to the World Health Organization. That number might be set to decrease, thanks in part to the scientific discoveries of a University of Utah biochemist.

Wesley Sundquist's lab at the U. laid the foundation for the development of a highly effective, long-lasting prophylactic — or preventive measure — against HIV, the virus that causes AIDS.

The resulting drug — lenacapavir — was developed by pharmaceutical company Gilead Sciences and has since been named the "Breakthrough of the Year" by Science, a top scientific journal.

Science described the drug as "a pivotal step toward diminishing HIV/AIDS as a global health crisis."

Although the U. wasn't responsible for developing the drug, Sundquist served as a consultant to Gilead Sciences, and his science was instrumental as the basis for creating lenacapavir.

Sundquist, a biochemist and chairman of the university's Department of Biochemistry, is involved in research focused on how HIV is built on a molecular level and how it interacts with the body to infect and spread through cells.

"The work goes back quite some time. We started in the late '90s," Sundquist said.

By purifying and analyzing the protein shell that surrounds the virus's genetic material, Sundquist's team discovered what the shell looks like and how it's put together.

In a crucial step, the research team found that the virus's shell is highly sensitive to changes. Making even small tweaks to the proteins that make up the shell stopped the virus from replicating as quickly, which suggested that drugs that affect the protein shell could prove to be effective.

It was these insights that caught the attention of Gilead Sciences, prompting the company to search for drugs that target HIV's protein shell — otherwise known as a capsid — tapping Sundquist as a consultant and eventually leading to the development of lenacapavir.

The drug itself binds the viral protein shell of HIV, preventing it from assembling properly and productively entering the nucleus of host cells.

"HIV is unusual because it has a cone-shaped capsid like an ice cream cone. It was of interest to understand how it can make a cone, and we were, of course, very curious about how proteins can assemble into a cone shape and also what that did for the virus," Sundquist said.

Unlike other HIV drugs, lenacapavir is noteworthy due to its potential for preventing HIV entirely.

"It's (lenacapavir is) very potent — but even more importantly, it's very long-lasting in humans," Sundquist said. "What we'd like to be able to do in a process called PrEP — pre-exposure prophylactics — is to prevent transmission from one person to another."

This has been difficult, Sundquist said, not because there aren't drugs already on the market that can prevent transmission, but because the existing drugs are not very long-lasting.

"People become noncompliant because it's hard to take drugs every single day for something that you don't yet have. The advantage of lenacapavir is it's a single shot that protects people for six months from getting the virus," Sundquist said. "It's something like a vaccine. It's a small molecule —not a vaccine, but it behaves the same way."

Especially in contexts where people have limited access to medical care, the longer duration of lenacapavir leads to a marked difference in outcomes.

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In fact, in large clinical trials in South Africa and Uganda — two HIV hot spots — not one of the more than 2,000 women who received a dose of lenacapavir contracted HIV over the course of the study.

"Lenacapavir almost completely prevents the transmission of HIV into at-risk populations," Sundquist said. "This is just an amazing result."

Follow-up trials in other populations, including men and people who identify as nonbinary, have further confirmed the drug's efficacy, Sundquist said.

Along with contributions to global health, Sundquist sees his lab's work being motivated primarily by discovery.

"We're driven by curiosity to discover things that we don't understand," he said. "It's not so different from other kinds of adventures. The same thing that drives people to climb mountains drives us to discover how molecular machines work."

Although Sundquist said that a big portion of the work on an HIV drug is now outside of the scope of his lab, he's excited for the future possibilities his work with Gilead Sciences leads to, hinting that the company thinks it could formulate the drug to last for a year.

Still, the work on HIV is far from over.

"We still need a vaccine. That would be even better because then you could give everyone the vaccine and protect everyone, not just at-risk individuals," Sundquist said. "That's been a very difficult problem."

Correction: A byline for a photo in a previous version incorrectly spelled Janet Iwasa's first name as Janey.

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