Outside the lab, others took notice. Tomas Cihlar, then principal scientist at pharmaceutical company Gilead Sciences, came across von Schwedler’s results and was struck by how critical the capsid seemed for viral function. He started investigating the capsid further. “Wes’s name was on most papers related to the HIV capsid,” he recalls.

In late 2005, the two met for the first time to discuss the capsid’s potential as a new drug target. “I was not sure how it would go, because Wes was already prominent in the HIV field and a very well recognized biochemist. But it turned out that he’s a really nice guy,” says Cihlar, now senior vice president of virology research at Gilead. That conversation launched a decades-long scientific partnership, with Sundquist acting as a basic science consultant on the structure of the capsid while Gilead worked to design a drug.

Academic labs like Sundquist’s are critical to drug development, Cihlar says. “Without investing in basic research, we in industry would not have the foundational information about biological functions and systems.”

Even with that foundation, developing a capsid-targeting drug wasn’t easy. Unlike for more conventional targets, no known compounds interacted with the capsid, and there was no roadmap to find them. The screening process demanded 50 grams of capsid protein—the equivalent of 400 million billion viral particles. And after four years, the initial screen failed. “We had to make our decision,” Cihlar reflects: “Are we going to walk away, or are we going to keep trying?”

They kept trying.

Starting from a new molecule that interacted very weakly with the capsid and was very unstable, Gilead researchers spent six years painstakingly synthesizing new molecules, making improvements over the course of more than 4,000 compounds made and tested individually. Finally, they arrived at a compound that bound the capsid protein and interfered sufficiently with viral replication. In addition, it was also incredibly stable, affording long dosing intervals.

In cells in a dish, in animal models, in pilot studies, the compound’s efficacy exceeded expectations. “There were multiple moments when I felt like: this is working better than we could ever imagine,” Cihlar recalls. 

HIV infects 1.3 million people every year. Despite treatment advances turning HIV infection from a death sentence into a largely manageable chronic condition for those with access to high-quality health care, over 600,000 people die from HIV/AIDS worldwide every year, many in southern and eastern Africa, where stigma and reduced access to health care can limit treatment options.

So that’s where lenacapavir was tested. The first large clinical trial recruited over 2,000 women in Uganda and South Africa, among the countries with the highest rates of HIV infection and death. Advocates like Yvette Raphael, co-founder and executive director of Advocacy for Prevention of HIV in Africa, were key to the study’s success. As chair of the advisory board, Raphael helped ensure that the most affected populations—young women, including those pregnant and breastfeeding—would be a focus.

Women came into the clinic for an injection every six months, and by the end of a year, not one of the trial participants had contracted HIV.

Follow-up trials in other populations, including men and nonbinary people, confirmed the drug’s efficacy. “Lenacapavir almost completely prevents the transmission of HIV into at-risk populations,” Sundquist says. “This is just an amazing result.” In June 2025, lenacapavir received FDA approval for HIV prevention.

“It’s one of those things that we’ve waited for,” Raphael says. “To get an injection twice a year that prevents you from contracting HIV, in places where HIV prevalence amongst young people is still so very high—it’s groundbreaking, and it’s almost likened to a miracle.”

The remarkable impact of the drug depends not only on how strongly it inhibits the virus, but also on how long it lasts. In regions where taking a daily pill might be difficult, a twice-a-year preventive injection could make a huge difference. 

Future work must prioritize disseminating information on lenacapavir, as well as the drug itself, to help at-risk communities make informed choices, Raphael says. But she’s hopeful that lenacapavir could dramatically change the course of, and eventually end, the HIV epidemic. “We’d like to see the rate of new infections drop to almost zero. And lenacapavir has shown that it has the possibility of getting us there much quicker.”

You never know where basic research will lead, Sundquist muses. A question founded in curiosity about the natural world can lead to a breakthrough that could change the trajectory of infections worldwide. 

But Sundquist says the future of lenacapavir is still up in the air. After two decades of basic science, industry collaboration, and clinical trials, changes to federal funding priorities mean that the programs that would have helped pay for the distribution of the drug to those who need it most are now in question. It’s uncertain how lenacapavir will make it past this final implementation step.

“The potential for treating or preventing infections relatively cheaply is there,” Sundquist emphasizes. “It would be a human tragedy if we don’t roll it out.”

Meanwhile, Sundquist continues to uncover basic biology and expand new networks of scientific collaboration.

Since 2007, Sundquist has run CHEETAH, an NIH-funded program that connects HIV-focused labs at the U and nationwide to build the foundations for further breakthroughs in HIV treatment and prevention. The 20-lab coalition helps researchers build partnerships and tackle broader challenges. 

As lenacapavir rolls out, the Sundquist lab’s more recent discoveries are setting the stage for future medicines. Sundquist and his “science buddy” Hill are uncovering features of the ESCRT pathway, a fundamental process that helps sort molecules inside cells, that suggest targets for broad-acting anticancer therapies. 

In other cases, their work has revealed the intricate beauty of natural processes, with the translational impact unknown… for now. “We don’t know what we don’t know,” Hill underscores, “but we do know there’s a lot of it. Even if you don’t quite know how it might become useful, you’ve got to find it out, because some of it will be transformative.”

“We’re driven by curiosity to discover things that we don’t understand,” Sundquist adds. “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.”

Sophia Friesen is a research communications manager for University of Utah Health.