Cell-based measures of viral persistence are associated with immune activation and programmed cell death protein 1 (PD-1)-expressing CD4+ T cells

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. We performed a comprehensive assessment of ultrasensitive plasma HIV RNA levels, cell-associated HIV RNA levels...

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Vydáno v:	The Journal of infectious diseases Ročník 208; číslo 1; s. 50
Hlavní autoři:	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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 01.07.2013
Témata:	Adult Antiretroviral Therapy, Highly Active CD4 Lymphocyte Count CD4-Positive T-Lymphocytes - immunology DNA, Viral - drug effects Female HIV - drug effects HIV Infections - drug therapy HIV Infections - immunology HIV Infections - virology Humans Immunity, Cellular - drug effects Lymphocyte Activation - drug effects Lymphocyte Activation - immunology Male Middle Aged Programmed Cell Death 1 Receptor - blood Proviruses - drug effects RNA, Viral - blood D-dimer 2-LTR circles HIV ongoing viral replication raltegravir intensification
ISSN:	1537-6613, 1537-6613
On-line přístup:	Zjistit podrobnosti o přístupu
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Popis
Shrnutí:	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. 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. 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). 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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1537-6613 1537-6613
DOI:	10.1093/infdis/jis630