Date: December 2, 2019 By:
The Ragon Institute of MGH, MIT and Harvard received $10 million from the Bill & Melinda Gates Foundation to move towards drug-free HIV remission.
HIV remains a major global health challenge, with UNAIDS reporting 37.9 million people living with HIV and 1.7 million new cases each year. Antiretroviral therapy (ART) allows people to suppress HIV viral load, thereby preventing both disease transmission and progression, with a daily pill. Though medical remission is a huge step forward, patients must remain on ART for the rest of their lives. Access to, and compliance with, daily treatments, particularly in resource poor countries, can be a barrier to effective HIV treatment and remains an issue for the duration of the patient’s life.
A New Grant
Xu Yu, M.D., Ragon Institute faculty member and Associate Professor of Medicine at Harvard Medical School and Bruce Walker, M.D., Director of the Ragon Institute and Director of the Harvard University Center for AIDS Research, have just received a $10 million HIV Reservoirs grant from the Bill & Melinda Gates Foundation to understand the biology of those infected cells (as “rebound-competent reservoirs”) that persist in the body despite antiretroviral treatment and contribute to the viral rebound after treatment interruption. Joined by Ragon associated members Mathias Lichterfeld (Brigham and Women’s Hospital and Harvard Medical School); Alex Shalek (MIT); Zaza Ndhlovu and Thumbi Ndung’u, (University of KwaZulu-Natal); Krista Dong (Massachusetts General Hospital), along with Steve Deeks (University of California-San Francisco) and Janet and Robert Silliciano (John Hopkins University) in a multidisciplinary, international effort, Yu’s team will discover how these viral reservoirs remain hidden while uncovering potential therapeutic targets in geographically and genetically diverse populations.
Reservoirs of Disease
HIV, like all retroviruses, inserts a copy of its genome into its host immune cells, such as CD4+ T-cells, monocytes, macrophages, and myeloid dendritic cells. Without ART, these infected cells produce copies of HIV which destroy the host cell and move on to infect new cells. In the presence of ART, some infected cells can persist long-term, but typically produce little or no virus at all, which makes them invisible to the immune system. However, upon cessation of the treatment, these cells could give rise to new virions and are responsible for the rebound of viremia. Such latently-infected cells are small in number, often hidden, difficult to identify, and cannot currently be successfully targeted by medication. Thus, these viral reservoirs persist indefinitely while on ART, necessitating continued treatment for the life of the patient.
Know Your Enemy
Yu and her team will use cutting-edge technologies to perform a detailed molecular characterization of these hidden cells. Using samples from both the USA and Africa, they will learn how these rebound-competent viral reservoirs change in response to long-term ART and what influence both geographic and genetic background of the patient has on the evolution of these viral reservoirs. A variety of genomic sequencing and immunological profiling techniques will identify biomarkers and immune responses unique to cells bearing rebound-competent viral genomes, revealing potential targets for therapeutic intervention. This thorough investigation will give insight into potential treatments targeted towards destroying, or permanently repressing, rebound-competent reservoirs, promoting a drug-free remission and removing the need for continuous, lifelong treatment in HIV+ individuals.
About the Ragon Institute
The Ragon Institute of MGH, MIT and Harvard was established in 2009 with a gift from the Phillip T. and Susan M. Ragon Foundation, creating a collaborative scientific mission among these institutions to harness the immune system to combat and cure human diseases. A primary focus of the institute has been to contribute to the development of an effective HIV vaccine. The Ragon Institute draws scientists and engineers from diverse backgrounds and areas of expertise across the Harvard and MIT communities and throughout the world to apply the full arsenal of scientific knowledge to understanding mechanisms of immune control and immune failure to benefit patients. For more information about the Ragon Institute, visit www.ragoninstitute.org.
For more information on Dr. Xu Yu’s research, please visit: http://www.ragoninstitute.org/portfolio-item/yu-lab/
For more information on Dr. Bruce Walker’s research please visit:
Image: an HIV-infected T cell, provided by Wikimedia.
This article appears on the Ragon Institute website with the permission of the author.
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