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J Clin Virol. 2012 Oct;55(2):114-20. doi: 10.1016/j.jcv.2012.06.017. Epub 2012 Jul 13.

Longitudinal changes in HIV-1-specific T-cell quality associated with viral load dynamic.

Author information

1
Institute of Virology, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany. claudia.dembek@helmholtz-muenchen.de

Abstract

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.

OBJECTIVES:

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

STUDY DESIGN:

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.

CONCLUSION:

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.

PMID:
22795599
DOI:
10.1016/j.jcv.2012.06.017
[Indexed for MEDLINE]

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