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Journal of Virology, July 2001, p. 6508-6516, Vol. 75, No. 14
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.14.6508-6516.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Decay Kinetics of Human Immunodeficiency Virus-Specific CD8+ T Cells in Peripheral Blood after Initiation of Highly Active Antiretroviral Therapy

Joseph P. Casazza,1 Michael R. Betts,1 Louis J. Picker,2 and Richard A. Koup1,*

Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas,1 and Department of Pathology, University of Oregon Health Science Center, Portland, Oregon2

Received 2 November 2000/Accepted 11 April 2001

We measured the longitudinal responses to 95 HLA class I-restricted human immunodeficiency virus (HIV) epitopes and an immunodominant HLA A2-restricted cytomegalovirus (CMV) epitope in eight treatment-naive HIV-infected individuals, using intracellular cytokine staining. Patients were treated with highly active antiretroviral therapy (HAART) for a median of 78 weeks (range, 34 to 121 weeks). Seven of eight patients maintained an undetectable viral load for the duration of therapy. A rapid decline in HIV-specific CD8+ T-cell response was observed at initiation of therapy. After an undetectable viral load was achieved, a slower decrease in HIV-specific CD8+ T-cell response was observed that was well described by first-order kinetics. The median half-life for the rate of decay was 38.8 (20.3 to 68.0) weeks when data were expressed as percentage of peripheral CD8+ T cells. In most cases, data were similar when expressed as the number of responding CD8+ T cells per microliter of blood. In subjects who responded to more than one HIV epitope, rates of decline in response to the different epitopes were similar and varied by a factor of 2.2 or less. Discontinuation of treatment resulted in a rapid increase in HIV-specific CD8+ T cells. Responses to CMV increased 1.6- and 2.8-fold within 16 weeks of initiation of HAART in two of three patients with a measurable CMV response. These data suggest that HAART quickly starts to restore CD8+ T-cell responses to other chronic viral infections and leads to a slow decrease in HIV-specific CD8+ T-cell response in HIV-infected patients. The slow decrease in the rate of CD8+ T-cell response and rapid increase in response to recurrent viral replication suggest that the decrease in CD8+ T-cell response observed represents a normal memory response to withdrawal of antigen.

* Corresponding author. Mailing address: Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75390-9113. Phone: (214) 648-2807. Fax: (214) 648-2431. E-mail: richard.koup{at}utsouthwestern.edu.

Journal of Virology, July 2001, p. 6508-6516, Vol. 75, No. 14
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.14.6508-6516.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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