In a new chapter of global HIV cure science, Cindy Gay, MD, MPH, a researcher at the Institute for Global Health and Infectious Diseases and the UNC HIV Cure Center, has launched one clinical trial, and plans to start the second in the next few months, designed to make infected cells visible to targeted immune clearing strategies.
“This is a moment of real momentum,” said Dr. Gay, professor of medicine in infectious diseases. We’re testing two promising approaches to expose and clear the HIV reservoir, and we’re doing it with partners who bring tremendous expertise. Each will bring us closer to understanding how HIV might one day be controlled without daily therapy.”
First Trial: A New Approach to an Old Problem
DELIVER-02—led scientifically by study chair David Margolis, MD, with co-chair Dr. Fredrick Sawe, MBChB, MMED at the Kenya Medical Research Institute/Walter Reed Project—confronts one of the toughest challenges in modern HIV treatment. The latent HIV reservoir is a small population of infected cells that persist despite effective antiretroviral therapy (ART). Applying innovative latency‑reversal strategies with engineered antibodies that target infected cells, in a new partnership spanning UNC, the U.S. Military HIV Research Program (MHRP), and leading research centers in Kenya with the Kenya Medical Research Institute and Moi University Clinical Research Center, could be a game changer.
“In people living with HIV, the virus can hide in cells, even when medications keep it under control,” said Gay, protocol principal investigator. When ART is stopped, this reservoir quickly rebounds, leading to active viremia. These antibodies connect HIV‑infected cells and T cells, enabling T cells to target killing of the newly revealed infected cells.”
The study will use highly engineered DART® (Dual Affinity Re-Targeting) molecules— called MGD014 and MGD020—created by biotechnology partner MacroGenics designed to attach to cells expressing HIV and simultaneously attach to a T-cell (the immune system’s soldier). In effect, the two are brought together so that the T-cell can kill the infected cell—targeting the persistent reservoir of HIV infection while leaving healthy cells alone.
“The idea is to wake up HIV virus in cells where it is hiding so HIV proteins are present on the outside of the cell and then bring in the DART antibodies to clear them,” Gay explained. This is a most promising way to directly target the HIV reservoir.”
The study will compare three groups of participants. One group receives only the DART antibodies while continuing standard ART. A second group receives a medication known to stimulate the HIV virus in some cells containing HIV along with the DART antibodies. A third group will receive the DART antibodies and undergo a temporary interruption of ART, to allow comparison of the two different strategies of reversing HIV latency. Participants who undergo treatment interruption for up to 8 weeks will be monitored weekly, with strict criteria for restarting ART. Previous studies by the Military HIV Research Program have shown that this approach can be conducted safely, without increasing the viral reservoir.
DELIVER-02 Launch With New Global Partnerships
“What excites me most about this work is that we’re not only testing a new way to target HIV-infected cells with reversing latency, we are doing it in partnership with incredibly capable, high‑volume research centers in Kenya.These sites see large numbers of people living with HIV and have tremendous expertise and research experience.”
Research centers in Kenya—the Kericho Clinical Research Center (KEMRI/Walter Reed), and the Moi University Clinical Research Centre (MUCRC) in Eldoret are joining UNC as clinical partners.
Gay traveled to the Kenyan sites in December, with Susan Pedersen, RN, clinical director of the Institute’s Global Clinical Trials Unit, to participate in study and site preparation and meet local teams. The trip was a resounding success and confirmed the study will greatly benefit from experienced and committed research teams at both Kenyan sites.
The study is funded by the U.S. Military HIV Research Program and National Institute of Allergy and Infectious Diseases. Biostatistical leadership comes from Jessica Keys, PhD, and Michael Hudgens, PhD, of the Institute’s CFAR Biostatistics Core.
Second Trial: A Parallel Innovation Breaking New Ground
Margolis and Gay are also launching the first‑in‑human study of IAP 086, a new latency‑reversing agent, The new drug could provide a safe, more potent way to more effectively activate hidden HIV.
For years, researchers have mostly relied on HDAC inhibitors like Vorinostat to try to reverse HIV latency, but these agents have often been too weak and, at higher doses, associated with side effects that limit their use. The new drug, IAP 086, takes a completely different approach, working through an alternative biological pathway to activate latent HIV within cells.
The study will include participants with well-controlled HIV, monitored in an inpatient clinical research unit after receiving the novel drug, to carefully monitor participant safety.
“HIV cure research has taught us that waking up hidden virus is possible, but our current tools are not powerful or safe enough,” said Margolis. “With this new drug, we’re taking a careful, stepwise approach—starting at very low doses, monitoring people intensively, and letting the safety data guide us.”
Behind all the technical detail is an unmistakably human story. For the past 18 months, Dr. Gay has been preparing for the two HIV cure studies while still caring for patients in clinic — the very people who motivate this work.
“Every step forward is about improving health and expanding choices for people living with HIV,” she said. “Reaching this point gives me hope and hopefully only the beginning of new strategies that get us closer to the goal.”