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Journal of Virology, December 2007, p. 13809-13815, Vol. 81, No. 24
0022-538X/07/$08.00+0     doi:10.1128/JVI.01566-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

A High Viral Burden Predicts the Loss of CD8 T-Cell Responses Specific for Subdominant Gag Epitopes during Chronic Human Immunodeficiency Virus Infection{triangledown}

Christof Geldmacher,1,2* Clive Gray,5 Martha Nason,2 Jeffrey R. Currier,4 Antelmo Haule,1 Lilian Njovu,1 Steffen Geis,1 Oliver Hoffmann,1 Leonard Maboko,1 Andreas Meyerhans,6 Josephine Cox,4 and Michael Hoelscher3

Mbeya Medical Research Programme, Referral Hospital, Mbeya, Tanzania,1 Vaccine Research Center, NIAID, NIH, Bethesda, Maryland,2 Department of Infectious Diseases and Tropical Medicine, University of Munich, 80799 Munich, Germany,3 The U.S. Military HIV Research Program, Rockville, Maryland 20851,4 National Institute for Communicable Diseases, Johannesburg, South Africa,5 Institute of Virology, University of Saarland, 66421 Homburg, Germany6

Received 18 July 2007/ Accepted 18 September 2007

Human immunodeficiency virus (HIV)-specific CD8 T-cell responses targeting products encoded within the Gag open reading frame have frequently been associated with better viral control and disease outcome during the chronic phase of HIV infection. To further clarify this relationship, we have studied the dynamics of Gag-specific CD8 T-cell responses in relation to plasma viral load and time since infection in 33 chronically infected subjects over a 9-month period. High baseline viral loads were associated with a net loss of breadth (P < 0.001) and a decrease in the total magnitude of the Gag-specific T-cell response in general (P = 0.03). Most importantly, the baseline viral load predicted the subsequent change in the breadth of Gag recognition over time (P < 0.0001, r2 = 0.41). Compared to maintained responses, lost responses were low in magnitude (P < 0.0001) and subdominant in the hierarchy of Gag-specific responses. The present study indicates that chronic exposure of the human immune system to high levels of HIV viremia is a determinant of virus-specific CD8 T-cell loss.

* Corresponding author. Present address: Vaccine Research Center, NIAID, Bethesda, MD 20892. Phone: (301) 594-8619. Fax: (301) 480-2779. E-mail: geldmacherc{at}mail.nih.gov

{triangledown} Published ahead of print on 26 September 2007.

Journal of Virology, December 2007, p. 13809-13815, Vol. 81, No. 24
0022-538X/07/$08.00+0     doi:10.1128/JVI.01566-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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