amfAR Greenlights New HIV Cure Studies with Grants Totaling $1.2 Million

Three researchers will test the ability of a pair of cancer drugs and broadly neutralizing antibodies to attack latent HIV, the main barrier to a cure.

July 18, 2024

Michael Peluso, MD, of the University of California, San Francisco (Photo courtesy UCSF)

amfAR has announced a slate of new grants awarded to researchers targeting the HIV reservoir, the main barrier to a cure. The grants were awarded to: Michael Peluso, MD, of the University of California, San Francisco; Adam Spivak, MD, of the University of Utah, Salt Lake City; and Yiming Yin, PhD, of Boston Children’s Hospital.

While many people living with HIV today and taking suppressive antiretroviral therapy consistently maintain low to undetectable levels of virus, cessation of treatment will in most cases cause latent HIV to activate and come roaring back. Eliminating the HIV reservoir is thus the holy grail of HIV cure research.

“These three projects are a reminder of the extraordinary ability of HIV to evade every attempt—other than a highly invasive stem cell transplant—to dislodge it from the reservoir,” amfAR CEO Kevin Robert Frost said. “We believe they will yield important new insights that bring us closer to a cure for all who need it.”

Adam Spivak, MD, of the University of Utah, Salt Lake City (Photo by Kristan Jacobsen Photography/University of Utah Health)

With a grant of $480,000, Dr. Peluso will test the ability of the drug N-803 to suppress HIV rebound in people after they have stopped antiretroviral therapy. N-803 is 25 times more potent than its natural immune hormone counterpart, IL-15, which has known anti-HIV activity. It appears to stimulate both natural killer (NK) and T cells and is already approved for use in the treatment of bladder cancer. Dr. Peluso will conduct a randomized clinical study of 18 people to test the ability of N-803 versus a placebo to suppress HIV following a planned treatment interruption. This approach has shown success in previous studies involving monkeys, but this will be the first trial to test the concept in humans.

Another $480,000 grant goes to Dr. Spivak to test the ability of another cancer drug, dasatinib, to reduce a person’s HIV reservoir. Dasatinib is used currently in the treatment of certain types of leukemia and blocks T cell proliferation, a fundamental mechanism of HIV persistence and control of HIV reservoir size. Previous case studies have shown it to be more effective than other treatments at reducing the size of the reservoir in people living with HIV. Dr. Spivak’s team will use blood samples from three ongoing clinical trials funded by the National Institutes of Health to test the effect of dasatinib on reservoir size, as well as other measures of immune function and viral diversity.

Yiming Yin, PhD, of Boston Children’s Hospital

Dr. Yiming Yin will use a grant of $240,000 to test a hypothesis that B cells, white blood cells that are a key part of the immune system, expressing antibodies capable of broadly neutralizing HIV variants could replace antiretroviral therapy and reduce the size of a person’s HIV reservoir. She will genetically engineer B cells with the ability to target three critical portions of the HIV envelope. Monkeys will be given these cells and then immunized with an mRNA vaccine expressing the HIV envelope; the function of those B cells will be assessed. Yin hopes to determine whether the B cells can suppress rebound of the HIV relative, simian-human immunodeficiency virus (SHIV), in SHIV-infected monkeys following treatment interruption.

“It’s no coincidence that two of these studies will test the effectiveness of FDA-approved cancer treatments for their anti-HIV activity,” amfAR senior scientific consultant Dr. Jeffrey Laurence said. “Time and again, we see parallels between HIV and cancer, and we hope the successful outcomes of these studies will lead to clinical benefits for people living with HIV.”