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J. Virol. doi:10.1128/JVI.02176-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

HLA Class I-Restricted T Cell Responses May Contribute to the Control of HIV Infection, but Such Responses are Not Always Necessary for Long-term Virus Control

Positive Health Program, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA; Division of Experimental Medicine, University of California, San Francisco, CA; Department of Epidemiology and Biostatistics, University of California, San Francisco, CA; Department of Microbiology and Immunology, University of California, Davis, CA

^* To whom correspondence should be addressed. Email: brinda.emu{at}ucsf.edu.

	Abstract

A rare subset of HIV-infected individuals maintains undetectable HIV RNA levels without therapy ("elite controllers"). To clarify the role of T cell responses in mediating virus control, we compared HLA Class I polymorphisms and HIV-specific T cell responses among a large cohort of elite controllers (HIV-RNA <75 copies/mL), "viremic" controllers (low-level viremia without therapy), "non-controllers" (high level viremia), and "antiretroviral therapy suppressed" individuals (undetectable HIV-RNA levels on antiretroviral therapy). The proportion of CD4+ and CD8+ T cells that produce interferon- and interleukin-2 in response to Gag and Pol peptides was highest in the elite and viremic controllers (p<0.0001). Forty percent of elite controllers were HLA-B*57 compared to 23% of viremic controllers and 9% of non-controllers (p<0.001). Other HLA Class I alleles more common in elite controllers included HLA-B*13, B*58, and B*81 (p<0.05 for each). Within elite and viremic controller groups, those with protective class I alleles had higher frequencies of Gag-specific CD8+ T cells compared to those without these alleles (p=0.01). Non-controllers, with or without protective alleles, had low-level CD8+ responses. Thus, certain HLA Class I alleles are enriched in HIV controllers and are associated with strong Gag-specific CD8+IFN+IL-2+ T cells. However, the absence of evidence of T cell-mediated control in many controllers suggests the presence of alternative mechanisms for viral control in these individuals. Defining mechanisms for virus control in "non-T cell controllers" might lead to insights into preventing HIV transmission, or preventing virus replication.

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