For more than 40 years, UCSF has been a leader in HIV research and care. Long before the idea of a cure was conceivable, UCSF scientists and clinicians helped pioneer antiretroviral therapy (ART), transforming HIV from a fatal diagnosis into a manageable chronic condition. UCSF pharmacists were essential to this shift, simplifying complex drug regimens, improving adherence, and helping patients navigate treatments that once required dozens of pills a day.

A new study published in Nature offers a hopeful glimpse into the next chapter of UCSF’s HIV legacy. This work, co-led by Amelia Deitchman, PharmD, PhD, an associate professor in the Department of Clinical Pharmacy, provided an in-depth study of a tested a combination immunotherapy approach paired with therapeutic vaccination, broadly neutralizing antibodies, and an immune-stimulating agent. The goal: To induce viral control without daily ART.

The collaborative clinical trial, conducted with UCSF School of Medicine colleagues Michael Peluso, MD, MHS, and Steven Deeks, MD, and with immunology analyses led by Rachel Rutishauser, MD, PhD, bridges bench science and clinical medicine across UCSF. Affiliated with the UCSF School of Pharmacy’s Drug Research Unit, a biomedical research and training program that also serves as a pharmacology core for the Center for Aids Research, the team is pushing the boundaries of what an HIV cure could look like.

Accelerating HIV control

At the UCSF Institute for Global Health Science’s 25th anniversary celebration, Deitchman highlighted that seven of the study’s 10 HIV+ participants maintained ART-free viral control after receiving the combination therapy and later pausing ART, an early but meaningful sign that sustained suppression without daily therapy may be achievable.

Deitchman explained that these studies increasingly focus on achieving ART-free remission — also known as a “functional cure” — which aims not to eliminate every HIV-infected cell but to empower the immune system to keep the virus suppressed without medication.

“It’s one of the more promising HIV cure studies, because there is evidence that there is some form of post-intervention control,” she said. “This is the first step in understanding what a phenotype of control could look like and what types of interventions might give way to that.”

A pharmacologist finds her purpose

Deitchman arrived at UCSF in 2018 as a clinical pharmacology fellow, joining one of the nation’s oldest HIV cohorts at Zuckerberg San Francisco General Hospital and Trauma Center. Under the mentorship of HIV pharmacology pioneer and clinical pharmacy professor Fran Aweeka, PharmD, and through collaborations with Timothy Henrich, MD, a UCSF Experimental Medicine professor, she found her focus in HIV persistence and cure science.

“At the time, some people had been looking at antiretroviral levels, but there were really few pharmacologists working on the clinical trials, and not a lot of pharmacologists with this expertise,” Deitchman said. "I developed my research program around that. I worked collaboratively with this study team on close to a dozen trials in the space of HIV cure, and that scope framework became the basis for the long COVID cohort that is also at General Hospital. UCSF is super collaborative. That’s the culture.” 

Immunology, pharmacology, and virology converge

To understand why some participants in the study achieved control, Deitchman’s team conducted viral rebound dynamic and pharmacokinetic/pharmacodynamic analyses alongside deep immunologic analyses with the Rutishauser Lab.  

“That analysis gave us this kind of complete picture of the pharmacology, the immunology, and the virology,” Deitchman said. “Higher broadly neutralizing antibody exposure was associated with delayed time to rebound, which we expected, but it wasn’t associated with the set point, which tells us other downstream immunologic changes are probably involved.” 

The next phase of the team’s work will examine how pharmacologic exposure to broadly neutralizing antibodies shapes immune control, and what combination strategies could bring the field closer to durable remission. 

Progress through persistence

Even as the political and funding landscape shifts, Deitchman remains optimistic about the future of HIV cure research. She said her recently funded National Institute on Drug Abuse grant, which will study HIV persistence among people who use methamphetamine, is an example of continuing momentum.

“For a very long time, there was not a lot of success in clinical trials,” she said. “This Nature study is very complimentary to a lot of other innovative studies all over the world that are looking at some similar interventions. I think there's just so much promise right now. The work and the investment is paying off.”

“We're all very committed to the work that we're doing, but things that are beyond our control change, and we have to find the best way forward,” she added. “We have to listen to what’s important in public health. Advocacy matters.”