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Pharmaceutical approaches to eradication of persistent HIV infection

Published online by Cambridge University Press:  11 February 2009

Mary-Catherine Bowman ,
Nancie M. Archin  and
David M. Margolis
Mary-Catherine Bowman
Affiliation:
Departments of Medicine, Microbiology & Immunology, and Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7435, USA.
Nancie M. Archin
Affiliation:
Departments of Medicine, Microbiology & Immunology, and Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7435, USA.
David M. Margolis*
Affiliation:
Departments of Medicine, Microbiology & Immunology, and Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7435, USA.
*
*Corresponding author: David Margolis, 3302 Michael Hooker Research Bldg, CB#7435, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7435, USA. Tel: +1 919 966 6388; Fax: +1 919 966 0584; E-mail: dmargo@med.unc.edu
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Abstract

Highly active antiretroviral therapy (HAART) has markedly decreased morbidity and mortality in human immunodeficiency virus type 1 (HIV-1)-infected individuals in the developed world. Successful therapy often results in stable plasma levels of HIV-1 RNA below the limits of detection of commercial assays. Nonetheless, HIV-1 has not been cured by HAART. The causes of persistence of HIV infection in the face of current therapy appear to be multifactorial: latent but replication-competent provirus in resting CD4+ T cells, cryptic viral expression below the limits of detection of clinical assays, and viral sanctuary sites might all contribute to persistence. Clearance of HIV infection will almost certainly require a multimodality approach that includes potent suppression of HIV replication, therapies that reach all compartments of residual HIV replication and depletion of any reservoirs of persistent, quiescent proviral infection. This review highlights the basic mechanisms for the establishment and maintenance of viral reservoirs and pharmaceutical approaches towards their elimination.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 11 , July 2009 , e6
Copyright
Copyright © Cambridge University Press 2009

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References

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Further reading, resources and contacts

Publications

Geeraert, L, Kraus, G, Pomerantz, RJ. (2008) Hide-and-seek: the challenge of viral persistence in HIV-1 infection. Annual Review of Medicine. 59, 487-501.CrossRefGoogle ScholarPubMed
Williams, S.A. and Greene, W.C. (2007) Regulation of HIV-1 latency by T-cell activation. Cytokine 39, 63-73CrossRefGoogle ScholarPubMed
Mok, H.P. and Lever, A.M. (2007) Chromatin, gene silencing and HIV latency. Genome Biol. 11, 228CrossRefGoogle Scholar
He, G., Ylisastigui, L. and Margolis, D.M. (2002) Chromatin Regulation of HIV-1 Expression. DNA and Cell Biology 21, 697-705CrossRefGoogle Scholar