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

Claudia J. Dembek*, Sarah Kutscher, Simone Allgayer, Carolina Russo, Tanja Bauer, Dieter Hoffmann, Frank D. Goebel, Johannes R. Bogner, Volker Erfle, Ulrike Protzer, Antonio Cosma

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)114-120
Number of pages7
JournalJournal of Clinical Virology
Volume55
Issue number2
DOIs
Publication statusPublished - Oct 2012
Externally publishedYes

Keywords

  • Correlates of protection
  • HIV
  • Longitudinal study
  • T-cell response

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