Longitudinal changes in HIV-1-specific T-cell quality associated with viral load dynamic.
BACKGROUND
Several correlates of HIV control have been described; however their predictive values remain unclear, since most studies have been performed in cross-sectional settings.


OBJECTIVE
We evaluated the cause and consequence relationship between quality of HIV-specific T-cell response and viral load dynamic in a temporal perspective.


METHODS
HIV-1-specific T-cell responses were monitored over 7 years in a patient that following treatment interruption maintained a stable/low viral set point for 3.1 years before control of viral replication was lost and antiretroviral therapy restarted.


RESULTS
We observed that high frequencies of HIV-1-specific CD4 and CD8 T cells were unable to prevent loss of viral control. Gradual loss of functionality was observed in these responses, characterized by early loss of IL-2, viral load-dependent decrease of IFN-γ and CD154 expression as well as increase of MIP-1β production. Terminally differentiated HIV-1-specific CD8 T cells expressing CD45RA were lost independently of viral load and preceded the loss-of-control phase of HIV infection.


CONCLUSIONS
By describing qualitative changes in HIV-1-specific T-cell responses that coincide with loss of viral control, we identified specific correlates of disease progression and putative markers of viral control. Our findings suggest including the markers IL-2, IFN-γ, MIP-1β, CD154 and CD45RA into monitoring of HIV-specific T-cell-responses to prospectively determine correlates of protection from disease-progression.
Institute of Virology, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany. claudia.dembek@helmholtz-muenchen.de
Claudia J
CJ
Dembek
Sarah
S
Kutscher
Simone
S
Allgayer
Carolina
C
Russo
Tanja
T
Bauer
Dieter
D
Hoffmann
Frank D
FD
Goebel
Johannes R
JR
Bogner
Volker
V
Erfle
Ulrike
U
Protzer
Antonio
A
Cosma
D019380:Anti-HIV Agents / Q000008:administration & dosage; D015415:Biomarkers; D023201:CD40 Ligand / Q000378:metabolism; D054407:Chemokine CCL4 / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008137:Longitudinal Studies; D011379:Prognosis; D013601:T-Lymphocytes / Q000276:immunology*; D019562:Viral Load; D028761:Withholding Treatment
D019380:Anti-HIV Agents; D015415:Biomarkers; D054407:Chemokine CCL4; D007376:Interleukin-2; D023201:CD40 Ligand; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens