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J. Virol. doi:10.1128/JVI.02164-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Antiviral Therapy During Primary SIV Infection Fails to Prevent Acute CD4+ T-cell Loss In Gut Mucosa But Enhances Their Rapid Restoration Through Central Memory T-cells

Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, CA

^* To whom correspondence should be addressed. Email: sdandekar{at}ucdavis.edu.

	Abstract

Gut associated lymphoid tissue (GALT) is an early target of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) and a site for severe CD4+ T-cell depletion. Although anti-retroviral therapy (ART) is effective in suppressing HIV replication and restoring CD4+ T-cells in peripheral blood, restoration in GALT is delayed. The role of restored CD4+ T-cell help in GALT during ART and its impact on anti-viral CD8+ T-cell responses have not been investigated. Using the SIV model, we investigated gut CD4+ T-cell restoration in infected macaques initiating ART during either the primary (1 week post-infection) stage, prior to acute CD4+ cell loss (PSI), or during chronic stage at 10 weeks post-infection (CSI). ART led to viral suppression in GALT and PBMC of PSI and CSI at comparable levels. CSI animals had incomplete CD4+ T-cell restoration in GALT. In PSI animals, ART did not prevent acute CD4+ T-cell loss by 2 weeks post-infection in GALT but supported rapid and complete CD4+ T-cell restoration thereafter. This correlated with an accumulation of central memory CD4+ T-cells and better suppression of inflammation. Restoration of CD4+ T-cells in GALT correlated with qualitative changes in SIV gag-specific CD8+ T-cell responses with a dominance of IL-2 producing responses in PSI animals, while both CSI macaques and untreated SIV infected controls were dominated by IFN- responses. Thus, central memory CD4+ T-cell levels and qualitative anti-viral CD8+ T-cell responses, independent of viral suppression, were the immune correlates of gut mucosal immune restoration during ART.