Decay kinetics of human immunodeficiency virus-specific CD8+ T cells in peripheral blood after initiation of highly active antiretroviral therapy

J. P. Casazza, M. R. Betts, Louis Picker, R. A. Koup

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6508-6516
Number of pages9
JournalJournal of Virology
Volume75
Issue number14
DOIs
StatePublished - 2001
Externally publishedYes

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Human immunodeficiency virus
Highly Active Antiretroviral Therapy
T-lymphocytes
deterioration
HIV
T-Lymphocytes
kinetics
therapeutics
blood
Cytomegalovirus
epitopes
Epitopes
viral load
Viral Load
HLA-A2 Antigen
Immunodominant Epitopes
Virus Diseases
Therapeutics
virus replication
half life

ASJC Scopus subject areas

  • Immunology

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Decay kinetics of human immunodeficiency virus-specific CD8+ T cells in peripheral blood after initiation of highly active antiretroviral therapy. / Casazza, J. P.; Betts, M. R.; Picker, Louis; Koup, R. A.

In: Journal of Virology, Vol. 75, No. 14, 2001, p. 6508-6516.

Research output: Contribution to journalArticle

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