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Characterizing the Latent HIV-1 Reservoir in Patients with Viremia Suppressed on cART: Progress, Challenges, and Opportunities

Author(s):

Jason W. Rausch* and Stuart F. J. Le Grice   Pages 1 - 15 ( 15 )

Abstract:


Modern combination antiretroviral therapy (cART) can bring HIV-1 in blood plasma to levels undetectable by standard tests, prevent the onset of acquired immune deficiency syndrome (AIDS), and allow a near-normal life expectancy for HIV-infected individuals. Unfortunately, cART is not curative, as within a few weeks of treatment cessation, HIV viremia in most patients rebounds to pre-ART levels. The primary source of this rebound, and the principal barrier to a cure, is the highly stable reservoir of latent, yet replication competent HIV-1 proviruses integrated into the genomic DNA of resting memory CD4+ T cells. In this review, prevailing models for how the latent reservoir is established and maintained, residual viremia and viremic rebound upon withdrawal of cART, and the types and characteristics of cell harboring latent HIV-1 will be discussed. Selected technologies currently being used to advance our understanding of HIV latency will also be presented, as will a perspective on which areas of advancement are most essential for producing the next generation of HIV-1 therapeutics.

Keywords:

HIV, latency, provirus, integration, residual viremia, antiretroviral, T cell, CD4, TCR, clonal expansion, homeostatic maintenance, multiple displacement amplification, MDA

Affiliation:

Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, National Institute of Health, Frederick, MD 21702, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, National Institute of Health, Frederick, MD 21702



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