UNC CARE scientists will explore improved approaches to attack latently infected cells, and augment antiviral responses to clear residual virus infection in the next five years. A new compound like AZD5582, but designed for use in humans, is expected to enter clinical testing early next year via Qura Therapeutics, the public-private partnership between UNC-Chapel Hill and ViiV Healthcare. Importantly, this research was then extended in a longitudinal, multi-dose study at Emory University in ART-suppressed rhesus macaques infected with Simian Immunodeficiency Virus (SIV). Published in “Nature,” this work was accomplished in ART-suppressed mouse models with fully functioning human immune cells, the kind typically infected with HIV in humans. Last year, UNC CARE scientists and collaborators used a compound called AZD5582 to activate latently infected CD4+ T cells at impressive levels in blood and many different tissues with no or very little toxicity. In collaboration with academic scientists and clinicians, industry investigators, and the community, UNC CARE plans to define new targets to destabilize proviral genomes that persist despite ART, define new approaches to block proviral establishment, develop and deploy new effectors to clear viral reservoirs, delineate effective strategies to prevent rebound viremia that might emanate from such reservoirs after ART is discontinued, and create bridges to the community to improve the understanding of and access to HIV cure research and clinical trials. “We will also pursue interventions to prevent rebound of viremia after interruption of antiretroviral therapy (ART), and we will leverage a broad portfolio of tools from both academic and industry partners, and apply new discoveries, demonstrating proof-of-concept for clinical initiatives.” “We will continue to pursue our central unifying hypothesis that reversing HIV latency will ultimately lead to eradication of persistent HIV infection,” Margolis said. CARE will now expand its expertise and work toward a better understanding of persistent HIV infection, the discovery of novel approaches to disrupt HIV latency, methods to clear the HIV reservoir, and identification of strategies to control viral rebound. Since its inception in 2011, the Martin Delaney Collaboratory program has made important advances towards a cure for HIV. David Margolis, professor of medicine at the UNC School of Medicine, director of the UNC HIV Cure Center. The Collaboratory of AIDS Researchers for Eradication, or CARE, which will receive $5.2 million for each of the next five years, was one of the two original collaboratory programs funded since the beginning, along with UC San Francisco. Additionally, one of the new grants is focused specifically on HIV cure research in infants and children. The new awards for the Martin Delaney Collaboratories for HIV Cure Research program, initiated in 2011, further expand the initiative’s 2016 renewal from six institutions to 10, and represent a funding increase of approximately 75%. The National Institutes of Health has awarded approximately $53 million in annual funding over the next five years to 10 research organizations in a continued effort to find a cure for HIV.
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