amfAR, The Foundation for AIDS Research

New Clues to the Nature of HIV Reservoirs

By Jeffrey Laurence, M.D.

Latent viral reservoirs remain a major obstacle to finding a cure for HIV. Understanding how latency is established, sustained, and reversed is critical to identifying new strategies to purge latently infected cells. In December, a number of amfAR-funded scientists reported some important findings regarding the nature of HIV reservoirs.

First, researchers led by ARCHE grantees Dr. Steven Deeks of the University of California, San Francisco and Dr. Sarah Palmer at the University of Sydney in Australia—joined by colleagues from Sweden and the National Institutes of Health—provide further hard data that the “primary barrier to a cure” is the persistence of an extraordinarily stable population of HIV-infected CD4+ memory T cells.

HIV T Cell 
An HIV-infected T cell. © 2009 National Institute of Allergy and Infectious Diseases

Writing in the December issue of the Proceedings of the National Academy of Sciences, they analyzed eight individuals after 4–12 years on suppressive combination antiretroviral therapy. They found that the size of the viral reservoir in each person differed: it was significantly smaller in those who began treatment early (within three months of probable infection). Additionally, they observed that the virus contained within the latently infected cells didn’t change genetically during the course of treatment, indicating only low or possibly even no replication. In the absence of active virus growth, Deeks, Palmer, and colleagues concluded that the reservoirs could be maintained indefinitely by normal cellular growth alone.

In another study, amfAR grantees Drs. Suha Saleh, Paul Cameron, and Sharon Lewin from Monash University in Melbourne, Australia and Dr. Rafick-Pierre Sekaly from the Vaccine and Gene Therapy Institute in Florida, examined some of the processes involved in the initial infection of CD4+ memory T cells. As documented in PLoS Pathogens, they found that direct cell-to-cell contact between the T cell and a minor type of white blood cell, the myeloid dendritic cell, was required. They also identified the genes involved. Their hope is that these dendritic cells and their genes may provide additional targets for interventions that will ultimately break the lock latent viral reservoirs have on an HIV cure.

Dr. Laurence is amfAR’s senior scientific consultant.