University of Utah Health researcher Wesley Sundquist, PhD, has recently gained global recognition after being named one of TIME magazine’s 100 most influential people in the world. This honor highlights the profound impact of his laboratory’s foundational research that ultimately led to the development of lenacapavir, a groundbreaking medication capable of preventing HIV infections with unprecedented efficacy. Sundquist’s work is a testament to how basic scientific inquiry can translate into monumental advances in global health.
Lenacapavir, developed in collaboration with the biopharmaceutical giant Gilead Sciences, represents a significant leap forward in HIV prevention. Unlike existing prophylactic treatments that require daily dosing, lenacapavir’s unique formulation allows for a single injection to confer protection for up to six months. This extended duration of efficacy stands to revolutionize patient compliance and accessibility, addressing longstanding challenges in the management and prevention of HIV transmission.
Clinical trials involving tens of thousands of participants have demonstrated that lenacapavir provides near-perfect protection against HIV infection, with efficacy rates reported between 99.9 and 100 percent. These remarkable results have been described by Sundquist as “spectacularly successful,” indicating a breakthrough not only in clinical outcomes but also in the pharmacodynamics and viral targeting mechanisms of antiretroviral therapy.
The genesis of lenacapavir traces back to decades of fundamental research in Sundquist’s laboratory, where the original mandate was not drug development, but rather an in-depth exploration of the structural biology of the HIV virus particle. Their meticulous work focused on elucidating the architecture and assembly process of HIV’s capsid, a protein shell that safeguards the viral RNA and orchestrates infection. This capsid was found to exhibit a sensitivity to perturbation that made it an ideal target for therapeutic intervention.
Central to Sundquist’s research was the discovery that the HIV capsid protein’s conformation is both critical for viral replication and uniquely susceptible to disruption by small molecules. This insight provided a strategic avenue for Gilead Sciences to develop lenacapavir as a capsid inhibitor, a drug class that interferes with multiple stages of the HIV lifecycle by destabilizing the viral core, thereby preventing infection of host cells and viral propagation.
Collaboration with Gilead Sciences was instrumental in translating Sundquist’s structural biology insights into a viable pharmaceutical agent. Tomáš Cihlář, PhD, Sundquist’s key collaborator at Gilead, shares in the prestigious recognition by TIME magazine, underscoring the power of academia-industry partnerships in accelerating drug discovery and development processes that directly impact public health.
Rachel Hess, MD, MS, Associate Vice President for Research at University of Utah Health, emphasizes that this achievement exemplifies how fundamental research creates the necessary environment for innovations that enhance health outcomes globally. This aligns with Sundquist’s own philosophy that while basic research is pursued to understand nature’s complexities, it simultaneously acts as the bedrock for revolutionary medical advances.
Bob Carter, MD, PhD, CEO of University of Utah Health, praises Sundquist’s work for its indelible contribution to medical science and human health. The translation of detailed molecular and structural findings into a treatment that prevents HIV transmission highlights the indispensable role of foundational science in formulating lifesaving therapies, particularly in the context of persistent global infectious diseases.
Sundquist reflects on the importance of scientific curiosity, noting that his team’s initial goal was to unravel the natural world’s mysteries, specifically HIV’s structural components, without immediate consideration for therapeutic outcomes. This organic process of discovery ultimately served as the “feedstock” for innovative medicine, illustrating the nonlinear pathway from knowledge generation to societal benefit.
The protective mechanism of lenacapavir centers on its ability to bind selectively to the HIV capsid protein, stabilizing it in a dormant state that precludes the virus from uncoating and replicating within host cells. This mode of action distinguishes lenacapavir from other antiretroviral drugs which primarily target viral enzymes such as reverse transcriptase or protease, opening new frontiers in HIV pharmacotherapy.
Ongoing studies continue to evaluate lenacapavir’s long-term safety and its integration into existing prevention strategies, including pre-exposure prophylaxis (PrEP) programs. The drug’s minimal dosing frequency not only has the potential to improve adherence but also reduces the burden on healthcare systems, particularly in regions with limited medical infrastructure and high HIV prevalence.
The anticipated broad distribution of lenacapavir could dramatically reduce new HIV infection rates worldwide, a historic advance in the fight against a virus that has claimed millions of lives. Sundquist and his team’s contributions underscore the profound societal impact that can arise from patient, curiosity-driven scientific investigation.
The full list of TIME100 honorees, including Dr. Wesley Sundquist and Dr. Tomáš Cihlář, will be featured in the April 28, 2025, issue of TIME magazine, which is available on newsstands and online at time.com/time100.
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Subject of Research: HIV structural biology and drug development
Article Title: Wesley Sundquist’s Fundamental Research Catalyzes Breakthrough HIV Prevention Drug lenacapavir
News Publication Date: April 18, 2025
Web References:
– https://medicine.utah.edu/faculty/wesley-i-sundquist
– https://healthcare.utah.edu/newsroom/news/2024/12/hiv-drug-based-research-sundquist-lab-sciences-2024-breakthrough-of-year
– https://www.linkedin.com/in/tomas-cihlar-09b45941/
– https://time.com/time100
Image Credits: David Titensor / University of Utah Health
Keywords: Human immunodeficiency virus, HIV infections, Basic research, HIV prevention, Structural biology
