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Dembek, C.J. ; Kutscher, S. ; Allgayer, S. ; Russo, C. ; Bauer, T. ; Hoffmann, D.* ; Goebel, F.D.* ; Bogner, J.R.* ; Erfle, V. ; Protzer, U. ; Cosma, A.

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

J. Clin. Virol. 55, 114-120 (2012)

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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-gamma and CD154 expression as well as increase of MIP-1 beta 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-gamma, MIP-1 beta, CD154 and CD45RA into monitoring of HIV-specific T-cell-responses to prospectively determine correlates of protection from disease-progression.

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