Progressive contraction of the latent HIV reservoir around a core of less-differentiated CD4⁺ memory T Cells.
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.
INSERM U1012, 94276 Le Kremlin-Bicêtre, France.
S
S
Jaafoura
INSERM U1012, 94276 Le Kremlin-Bicêtre, France.
M G
MG
de Goër de Herve
Systems Medicine of Infectious Diseases, Helmholtz Centre for Infection Research, Inhoffenstraße 7, 38124 Braunschweig, Germany.
E A
EA
Hernandez-Vargas
INSERM U1012, 94276 Le Kremlin-Bicêtre, France.
H
H
Hendel-Chavez
INSERM U1012, 94276 Le Kremlin-Bicêtre, France.
M
M
Abdoh
INSERM U1012, 94276 Le Kremlin-Bicêtre, France.
M C
MC
Mateo
1] INSERM U996, 92140 Clamart, France [2] Faculté de Médecine, Université Paris-Sud, 94276 Le Kremlin-Bicêtre, France.
R
R
Krzysiek
Department of Medicine, Institut Gustave Roussy, 94805 Villejuif, France.
M
M
Merad
INSERM U1018, 94275 Le Kremlin-Bicêtre, France.
R
R
Seng
1] INSERM U1012, 94276 Le Kremlin-Bicêtre, France [2] Faculté de Médecine, Université Paris-Sud, 94276 Le Kremlin-Bicêtre, France.
M
M
Tardieu
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.
J F
JF
Delfraissy
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.
C
C
Goujard
1] INSERM U1012, 94276 Le Kremlin-Bicêtre, France [2] Faculté de Médecine, Université Paris-Sud, 94276 Le Kremlin-Bicêtre, France.
Y
Y
Taoufik
D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology / Q000821:virology*; D002454:Cell Differentiation / Q000502:physiology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D018450:Disease Progression; D004197:Disease Reservoirs; D015658:HIV Infections / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D016176:T-Lymphocyte Subsets / Q000473:pathology / Q000821:virology; D013997:Time Factors; D019562:Viral Load; D017735:Virus Latency / Q000502:physiology*
D044966:Anti-Retroviral Agents