A trial led by Joe Eron, MD, a researcher with the UNC Institute for Global Health and Infectious Diseases, marks a significant milestone toward what could become the first complete long‑acting HIV regimen requiring dosing only twice per year. This new report is considered the first Phase 2 study to evaluate a complete HIV‑1 treatment regimen that is administered once every six months for people already on treatment who are switching from daily oral ART.
Chapel Hill, NC — A new study published in The Lancet Microbe reports the first twice‑yearly injectable HIV treatment regimen–combining lenacapavir, teropavimab, and zinlirvimab—has achieved high rates of viral suppression and demonstrated a favorable safety profile at 26 weeks. Led by Joe Eron, MD, a researcher with the UNC Institute for Global Health and Infectious Diseases, the findings mark a significant milestone toward what could become the first complete long‑acting HIV regimen requiring dosing only twice per year. 
Conducted across 34 clinical sites in the U.S., Canada, Australia, and Puerto Rico, including the UNC Clinical Trials Unit in Chapel Hill, the Phase 2 randomized, open‑label study enrolled adults living with HIV-1 who were already virologically suppressed and whose virus was highly susceptible to the two broadly neutralizing antibodies (bNAbs) teropavimab and zinlirvimab. Participants either switched to the twice‑yearly injectable regimen or continued their daily oral antiretroviral therapy (ART).
“While lenacapavir alone has been studied for prevention or multidrug‑resistant HIV, and some broadly neutralizing antibodies have been tested in small or early‑phase studies, no complete combination regimen suitable for maintenance therapy with twice‑yearly dosing had ever reached Phase 2 evaluation,” said Dr. Eron, the Herman and Louise Smith Distinguished Professor of Medicine and Chief of UNC’s Infectious Diseases.
Strong Efficacy Comparable to Daily Oral Therapy
At week 26, 96% of participants who received the twice‑yearly injections maintained viral suppression — matching the suppression rate of participants who continued daily oral ART. Only one participant in the injectable group experienced confirmed viral rebound, and ultimately resuppressed without changing treatment, underscoring the regimen’s overall robustness.
The investigational combination was well tolerated, with no drug‑related serious adverse events, no grade 3 or higher treatment‑related effects, and no discontinuations due to safety concerns. The most common side effects were mild injection‑site reactions, consistent with expectations for long‑acting injectables. No infusion‑related reactions to teropavimab or zinlirvimab were reported.
Participants receiving the twice‑yearly regimen reported improvements in treatment satisfaction and quality of life. Notably, 84% expressed a preference for the injectable regimen over daily pills, suggesting strong patient interest in long‑acting treatment alternatives.
Major Step Toward Ultra‑Long‑Acting HIV Therapy
“These results reinforce the potential of lenacapavir paired with two broadly neutralizing antibodies to transform HIV treatment,” Dr. Eron said. “A twice‑yearly regimen could offer a meaningful alternative for people who face challenges with daily adherence or who simply prefer less frequent dosing.”
The investigational combination — the longest‑acting HIV treatment regimen tested to date — will continue to be evaluated in ongoing and future Phase 3 studies. The Phase 2 trial was funded by Gilead Sciences and is registered at ClinicalTrials.gov (NCT05729568).
About the Institute for Global Health and Infectious Diseases
Established in 2007, the UNC Institute for Global Health & Infectious Diseases at the University of North Carolina at Chapel Hill started over 30 years ago with infectious disease physician researchers at the UNC School of Medicine, studying HIV in China and Malawi. Through the years, our work has expanded to include emerging pathogens, cancer, women’s health and vector-borne disease like malaria–shaping policy through evidence-based research around the world. At UNC-Chapel Hill, the Institute facilitates research excellence while nurturing emerging scientists to advance patient care and practice, addressing the most important global health issues of our time–through research, training and service.