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Nat Commun. 2014 Nov 10;5:5407. doi: 10.1038/ncomms6407.

Progressive contraction of the latent HIV reservoir around a core of less-differentiated CD4⁺ memory T Cells.

Author information

1
INSERM U1012, 94276 Le Kremlin-Bicêtre, France.
2
Systems Medicine of Infectious Diseases, Helmholtz Centre for Infection Research, Inhoffenstraße 7, 38124 Braunschweig, Germany.
3
1] INSERM U996, 92140 Clamart, France [2] Faculté de Médecine, Université Paris-Sud, 94276 Le Kremlin-Bicêtre, France.
4
Department of Medicine, Institut Gustave Roussy, 94805 Villejuif, France.
5
INSERM U1018, 94275 Le Kremlin-Bicêtre, France.
6
1] INSERM U1012, 94276 Le Kremlin-Bicêtre, France [2] Faculté de Médecine, Université Paris-Sud, 94276 Le Kremlin-Bicêtre, France.
7
1] INSERM U1012, 94276 Le Kremlin-Bicêtre, France [2] Faculté de Médecine, Université Paris-Sud, 94276 Le Kremlin-Bicêtre, France [3] Department of Internal Medicine, Hôpitaux Universitaires Paris-Sud, 94275 Le Kremlin-Bicêtre, France.
8
1] Faculté de Médecine, Université Paris-Sud, 94276 Le Kremlin-Bicêtre, France [2] Department of Medicine, Institut Gustave Roussy, 94805 Villejuif, France [3] Department of Internal Medicine, Hôpitaux Universitaires Paris-Sud, 94275 Le Kremlin-Bicêtre, France.

Abstract

In patients who are receiving prolonged antiretroviral treatment (ART), HIV can persist within a small pool of long-lived resting memory CD4(+) T cells infected with integrated latent virus. This latent reservoir involves distinct memory subsets. Here we provide results that suggest a progressive reduction of the size of the blood latent reservoir around a core of less-differentiated memory subsets (central memory and stem cell-like memory (TSCM) CD4(+) T cells). This process appears to be driven by the differences in initial sizes and decay rates between latently infected memory subsets. Our results also suggest an extreme stability of the TSCM sub-reservoir, the size of which is directly related to cumulative plasma virus exposure before the onset of ART, stressing the importance of early initiation of effective ART. The presence of these intrinsic dynamics within the latent reservoir may have implications for the design of optimal HIV therapeutic purging strategies.

PMID:
25382623
PMCID:
PMC4241984
DOI:
10.1038/ncomms6407
[Indexed for MEDLINE]
Free PMC Article

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