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.
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.
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