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- Title
Cell-based measures of viral persistence are associated with immune activation and programmed cell death protein 1 (PD-1)-expressing CD4+ T cells.
- Authors
Hatano, Hiroyu; Jain, Vivek; Hunt, Peter W; Lee, Tzong-Hae; Sinclair, Elizabeth; Do, Tri D; Hoh, Rebecca; Martin, Jeffrey N; McCune, Joseph M; Hecht, Frederick; Busch, Michael P; Deeks, Steven G
- Abstract
<bold>Background: </bold> Studies aimed at defining the association between host immune responses and human immunodeficiency virus (HIV) persistence during therapy are necessary to develop new strategies for cure.<bold>Methods: </bold> We performed a comprehensive assessment of ultrasensitive plasma HIV RNA levels, cell-associated HIV RNA levels, proviral HIV DNA levels, and T cell immunophenotyping in a cohort of 190 subjects in whom HIV levels were suppressed by highly active antiretroviral therapy.<bold>Results: </bold> The median CD4(+) T cell count was 523 cells/mm(3), and the median duration of viral suppression was 31 months. Cell-associated RNA and proviral DNA levels (but not ultrasensitive plasma HIV RNA levels) were positively correlated with frequencies of CD4(+) and CD8(+) T cells expressing markers of T-cell activation/dysfunction (CD38, HLA-DR, CCR5, and/or programmed cell death protein 1 [PD-1]) (P < .05). Having a low CD4(+) T-cell count despite receipt of virologically suppressive therapy was associated with high cell-associated RNA and proviral DNA levels (P < .01) and higher frequencies of CD4(+) T cells expressing CD38, HLA-DR, CCR5, and/or PD-1 (P < .0001).<bold>Conclusions: </bold>Cell-based measurements of viral persistence were consistently associated with markers of immune activation and the frequency of PD-1-expressing CD4(+) T cells. Treated patients with a low CD4(+) T-cell count had higher frequencies of PD-1-expressing CD4(+) T cells and cell-based measures of viral persistence, suggesting that HIV infection in these individuals may be more difficult to cure and may require unique interventions.
- Publication
Journal of Infectious Diseases, 2013, Vol 208, Issue 1, p50
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jis630