amfAR Awards More than $1.6 Million in New Grants
Researchers will investigate the potential of current drugs and future technologies to cure HIV
In June 2022, amfAR awarded more than $1.6 million in new grants to five research teams aiming to eradicate the HIV reservoir—the main barrier to a cure.
The largest of the new grants, worth $1 million, was awarded to Xu Yu, M.D., of Massachusetts General Hospital in Boston. Dr. Yu will study 50 people who have been on antiretroviral therapy (ART) for at least 15 years and describe the loss of replication-competent viruses and relative accumulation of viruses in so-called gene deserts to determine if HIV has been cleared.
“Dr. Yu’s recent findings point to the intriguing possibility that a small fraction of people might have cleared HIV infection without realizing it,” amfAR CEO Kevin Robert Frost said. “If that’s true, it would not only be life-changing for the fortunate participants in this study, but would also renew hope for the millions of people taking ART that their treatment may not need to be lifelong.”
While Dr. Yu’s grant will describe the upshot of the past fifteen years or more of effective combination ART, Qigui Yu, M.D. Ph.D., of Indiana University in Indianapolis, will receive a grant of $100,000 to test a class of drugs approved to treat cancer to eradicate HIV-infected T follicular helper (Tfh) cells. Tfh cells usually function to educate B cells in making the most appropriate antibodies to fight infection. But when HIV-infected, Tfh cells may play a significant role in spreading infection, given their position in the lymph node, in proximity to other immune cells. Dr. Yu will test several compounds in a class of drugs that inhibit the protein BIRC5, whose usual function is to keep cells alive, and see if these BIRC5 inhibitors will allow infected Tfh cells to die.
Finally, in a nod to the promise of future technologies, three grants will explore a variety of gene therapies to eliminate HIV-infected cells. Saar Gill, Ph.D., of the University of Pennsylvania in Philadelphia, will receive $180,000 to design a transplant intervention for individuals living with HIV using a person’s own gene-edited cells. Before the transplant, Dr. Gill plans a series of immunotherapy and gene therapy interventions that would eliminate most or perhaps all of the viral reservoir. The transplanted cells will be gene-edited to protect them from HIV infection. After the transplant, he will use chimeric antigen receptor (CAR)-T cell immunotherapy to help clear out the remainder of the original immune system, which might still harbor HIV. This process will be tested in a small animal model.
With a $148,500 grant, Keith Jerome, M.D., Ph.D., of the University of Washington in Seattle, will study whether or not the presence of ART might adversely impact the efficacy of one of the most widely used means of delivering gene therapy—adeno-associated virus (AAV). Individuals who receive gene therapy most likely will be taking ART, so the question of compatibility is a vital one.
Anjie Zhen, Ph.D., of the University of California, Los Angeles will use a $210,000 grant to fine-tune CAR-T cell therapy, which has shown limited success against HIV. Dr. Zhen will create stems cells using blood-derived stem cells, selected for their potential to persist and self-renew. She will explore their capacity to mature into not only CAR-T cells, but also CAR-natural killer cells and CAR-macrophages, all three of which have the potential to attack HIV-infected cells.