Journal Article

HIV-Specific CD4<sup>+</sup> T Cells May Contribute to Viral Persistence in HIV Controllers

Peter W. Hunt, Hiroyu Hatano, Elizabeth Sinclair, Tzong-Hae Lee, Michael P. Busch, Jeffrey N. Martin, Joseph M. McCune and Steven G. Deeks

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 52, issue 5, pages 681-687
Published in print March 2011 | ISSN: 1058-4838
Published online March 2011 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1093/cid/ciq202
HIV-Specific CD4+ T Cells May Contribute to Viral Persistence in HIV Controllers

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Background. Human immunodeficiency virus (HIV)–-infected individuals maintaining plasma HIV RNA levels <75 copies/mL in the absence of therapy (“HIV controllers”) often maintain high HIV-specific T cell responses, which likely contribute to the control of viral replication. Despite robust immune responses, these individuals never eradicate HIV infection. We hypothesized that HIV-specific CD4+ T cells might serve as target cells for HIV, contributing to viral persistence in this setting.

Methods. We measured frequencies of activated (CD38+ HLA-DR+) and HIV Gag-specific CD4+ and CD8+ T cells and plasma- and cell-associated levels of HIV RNA and DNA in a cohort of 38 HIV controllers.

Results. Although there was no evidence of a relationship between the extent of low-level viremia and the frequency of either activated or HIV-specific CD4+ T cells, controllers with higher HIV-specific CD4+ T cell frequencies had higher cell-associated HIV DNA levels (ρ = 0.53; P = .019). Higher activated CD4+ T cell frequencies were also associated with higher levels of cell-associated DNA (P = .027) and RNA (P = .0096). However, there was no evidence of a relationship between cell-associated HIV RNA or DNA levels and HIV-specific CD8+ T cell frequencies.

Conclusions. These data support a model in which strong HIV-specific CD4+ T cell responses in HIV controllers, while contributing to a potent adaptive immune response, may also contribute to viral persistence, preventing the natural eradication of HIV infection.

Journal Article.  4193 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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