By Bunmi Yekini
The trio behind a major leap in HIV prevention — the creation of a long-acting injectable drug that nearly eliminates the risk of infection — has been honored with the 2025 Mani L. Bhaumik Breakthrough of the Year Award by the American Association for the Advancement of Science (AAAS).
The award recognizes Dr. Wesley Sundquist, a biochemist at the University of Utah; Dr. Moupali Das, vice president at Gilead Sciences; and Yvette Raphael, a South African community advocate and director of Advocacy for Prevention of HIV in Africa, for their collective work in bringing lenacapavir to life — the first drug to provide six-month HIV protection with a single injection.
“These individuals represent the three arms of what is necessary to create new science and then translate it for the world in a way that is really able to make a difference,” said Dr. Megan Ranney, dean of Yale School of Public Health and a member of the award selection committee.
The drug, derived from research into HIV’s cone-shaped capsid protein, was named Science journal’s 2024 Breakthrough of the Year. It marks a near-vaccine-level protection, achieving 100% efficacy in one clinical trial and 96% in another.
“This drug is extraordinary — the closest thing to a vaccine that we have,” said Ranney. “It’s beyond the wildest dreams of what many of us could have imagined.”
From Bench to Breakthrough
The drug’s journey began in the early 1990s when Sundquist, newly appointed at the University of Utah, focused his lab on the then-overlooked HIV capsid. In 1996, he published groundbreaking research mapping the protein’s architecture. His 2003 study showed that disrupting the capsid could stop viral replication.
“That was unexpected,” Sundquist said. “We wanted to work on an aspect of the problem that was unique.”
It wasn’t long before Gilead Sciences took interest. The company’s team, led by virologist Tomas Cihlář and chemist John Link, spent over a decade developing a compound that could inhibit the capsid. The result was lenacapavir — a drug with long-lasting effects, ideal for people who struggle with daily HIV medications.
“We sometimes think about industry as not having staying power,” said Ranney. “But it was something like 15 years here — fits and starts — and Gilead as an institution kept supporting capsid inhibitors.”
Designing Inclusive Trials
Das, a trained physician, led the pivotal clinical trials that helped prove lenacapavir’s value not just for treatment, but also for prevention.
“I remember seeing results from the first treatment study and thinking this drug might be very good for prevention too,” said Das. “I was immediately thinking: how could we use this for prevention?”
She spearheaded the PURPOSE 1 and 2 trials — two of the most inclusive and extensive HIV prevention studies ever conducted. PURPOSE 1 focused on adolescent girls and women in sub-Saharan Africa. Its results were so compelling the trial was stopped early in 2024, after showing 100% protection from infection.
“It was so exciting to have the first results for lenacapavir for HIV prevention be in women,” said Das.
PURPOSE 2 included participants from underrepresented regions, including Latin America, Southeast Asia, and the U.S. Results showed a 96% reduction in new infections.
‘The Human Voice Matters’
Raphael’s role as a bridge between the scientific community and those most impacted by HIV was crucial. As Chair of the PURPOSE 1 Advisory Board, she fought to ensure pregnant women, adolescents, and marginalized communities were included from the outset.
“We knew past trials had made mistakes,” said Raphael. “We wanted young people to be part so that the drug could be approved for them from the start.”
Her advocacy helped build trust within communities that had long been left out of HIV research.
“The human voice matters as much as the science to get to translation in the real world,” said Ranney. “Yvette’s leadership is a gorgeous exemplar of how great science is done.”
Raphael described her partnership with Das as a powerful collaboration. “We called her the ‘Das-rupter,’” she said. “Every time, we said we’d do better. I think with Moupali, this is the best we have done.”
An Uncertain Future
Despite its success, lenacapavir’s global distribution could be hampered by stalled funding — particularly as the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) faces legislative uncertainty.
“The logical funding for distributing lenacapavir in the developing world would come from PEPFAR,” said Sundquist. “But it is now basically on life support. That means this drug is at risk of not reaching those who need it the most.”
Raphael warned that future breakthroughs depend on sustained support. “Without continuous funding for prevention and advocacy, we won’t have tomorrow’s breakthroughs,” she said.
Still, the 2025 Breakthrough of the Year highlights a rare success in the long war against HIV — a drug made possible not only by science, but also by persistence, industry backing, and the power of community voices.