HIV DNA subspecies persist in both activated and resting memory CD4+ T cells during antiretroviral therapy

Murray, John M., Zaunders, John J., McBride, Kristin L., Xu, Yin, Bailey, Michelle, Suzuki, Kazuo, Cooper, David A., Emery, Sean, Kelleher, Anthony D. and Koelsch, Kersten K. (2014) HIV DNA subspecies persist in both activated and resting memory CD4+ T cells during antiretroviral therapy. Journal of Virology, 88 6: 3516-3526. doi:10.1128/JVI.03331-13

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Author Murray, John M.
Zaunders, John J.
McBride, Kristin L.
Xu, Yin
Bailey, Michelle
Suzuki, Kazuo
Cooper, David A.
Emery, Sean
Kelleher, Anthony D.
Koelsch, Kersten K.
Title HIV DNA subspecies persist in both activated and resting memory CD4+ T cells during antiretroviral therapy
Formatted title
HIV DNA subspecies persist in both activated and resting memory CD4+ T cells during antiretroviral therapy
Journal name Journal of Virology   Check publisher's open access policy
ISSN 1098-5514
0022-538X
Publication date 2014-03-01
Year available 2014
Sub-type Article (original research)
DOI 10.1128/JVI.03331-13
Open Access Status DOI
Volume 88
Issue 6
Start page 3516
End page 3526
Total pages 11
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Language eng
Formatted abstract
The latent HIV reservoir is a major impediment to curing HIV infection. The contribution of CD4+ T cell activation status to the establishment and maintenance of the latent reservoir was investigated by enumerating viral DNA components in a cohort of 12 individuals commencing antiretroviral therapy (ART) containing raltegravir, an integrase inhibitor. Prior to ART, the levels of total HIV DNA were similar across HLA-DR+ and HLA-DR− (HLA-DR±) CD38± memory CD4+ T cell phenotypes; episomal two-long terminal repeat (2-LTR) HIV DNA levels were higher in resting (HLA-DR− CD38−) cells, and this phenotype exhibited a significantly higher ratio of 2-LTR to integrated HIV DNA (P = 0.002). After 1 year of ART, there were no significant differences across each of the memory phenotypes of any HIV DNA component. The decay dynamics of integrated HIV DNA were slow within each subset, and integrated HIV DNA in the resting HLA-DR− CD38− subset per mm3 of peripheral blood exhibited no significant decay (half-life of 25 years). Episomal 2-LTR HIV DNA decayed relative to integrated HIV DNA in resting cells with a half-life of 134 days. Surprisingly, from week 12 on, the decay rates of both total and episomal HIV DNA were lower in activated CD38+ cells. By weeks 24 and 52, HIV RNA levels in plasma were most significantly correlated with the numbers of resting cells containing integrated HIV DNA. On the other hand, total HIV DNA levels in all subsets were significantly correlated with the numbers of HLA-DR+ CD38− cells containing integrated HIV DNA. These results provide insights into the interrelatedness of cell activation and reservoir maintenance, with implications for the design of therapeutic strategies targeting HIV persistence.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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