PHILADELPHIA – HIV researchers at the Perelman School of Medicine at the University of Pennsylvania and The Wistar Institute will co-lead a five-year, $23 million grant from the National Institutes of Health, as part of the second iteration of the Martin Delaney Collaboratory: Towards an HIV-1 Cure program, that aims to advance basic medical science toward a cure for the disease.

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James L. Riley, PhD,aresearch associate professor of Microbiology at the Perelman School of Medicine, and Luis J. Montaner, DVM, DPhil, director of the HIV-1 Immunopathogenesis Laboratory at The Wistar Institute Vaccine Center, will serve as co-principal investigators for the “BEAT-HIV: Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy” consortium, which includes 30 top HIV researchers from institutions across the nation, half of whom hail from Penn.

The scientific team will work with government, non-profit, and industry partners to test combinations of several novel immunotherapies and gene therapies under new preclinical research and clinical trials. Other institutions include Philadelphia FIGHT, Rockefeller University, VA San Diego Healthcare System, Johns Hopkins University, the University of Nebraska-Lincoln, and the University of Utah.

“This diverse, talented group of HIV researchers brings a wide array of expertise, perspectives, and resources to the table,” Riley said. “We’re honored to help lead this collaboration with the NIH and Delaney program’s support, and continue to investigate the promising immuno and gene therapy approaches developed and tested here at Penn and Wistar, among the other innovative areas of research the team is pursuing.”

The Philadelphia-based project is one of six grants awarded by the Delaney initiative totaling $150 million over the next five years. In 2010, National Institute of Allergy and Infectious Diseases (NIAID) established the Martin Delaney Collaboratory program in honor of the late HIV/AIDS activist Martin Delaney, a skilled and passionate advocate for cure research who served on the NIAID AIDS Research Advisory Committee. The collaboratory program supports international HIV cure research networks and encourages collaborative efforts to address the multifaceted puzzle of curing HIV.

While the scientific community knows far more about HIV/AIDS since the disease was first reported more than 35 years ago, a cure remains elusive in large part because HIV has the ability to establish a reservoir in the body by inserting its genetic material into that of immune cells that have a long lifespan.

The virus remains in these cells in a latent state, invisible to the immune system and to anti-HIV therapies. ART only targets HIV when it is actively replicating, so the treatment can never clear the cells containing the latent, non-replicating virus from an infected individual’s blood and tissues. If an individual discontinues ART, the virus emerges from these cells and reconstitutes a widespread infection. Tackling this problem therefore requires experts with expansive knowledge of HIV pathology, genetics and the immune system.

“The lifelong stigma, economic burden on society, strain on healthcare resources, and sheer toll on human life across the globe makes finding a cure a top priority,” Montaner said. “Together we’re building on our teams’ extensive established efforts to move forward and make those next transformative steps that will bring us closer to an HIV cure.”

The Philadelphia-lead BEAT HIV consortium will embark on three research projects.

The first area of study will identify where and how HIV hides so researchers can better assess if proposed clinical strategies can eradicate the virus. The second focuses on stimulating the immune system with which we are all born (innate immunity) through a combination immunotherapy approach using highly-potent antibodies against HIV together with pegylated interferon alpha 2b.

The third area of study will bring together two promising gene therapy strategies pioneered at Penn Medicine with the goal of engineering, growing and administering HIV resistant T cells that are uniquely empowered to find and destroy HIV-infected cells. The proposed gene therapy strategy leverages the advances made by Penn’s chimeric antigen receptor [CAR] T-cell therapy to treat cancer patients.

“It’s our belief that combining effective immunotherapies to treat HIV infected individuals will get us closer to finding an effective and lasting way to eliminate the need for lifelong ART – and ultimately accelerate the pace toward a cure,” Riley said.

Other Penn researchers include Faten Aberra, Katharine Bar, Michael Betts, Frederic Bushman, Susan Ellenberg, Ian Frank, Beatrice Hahn, George Shaw, Julie Jadlowsky, Carl June, David Metzger, Pamela Shaw, Pablo Tebas, and E. John Wherry.

To view the full NIH release, click here.

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