Decay Kinetics of Human Immunodeficiency Virus-Specific CD8+T Cells in Peripheral Blood after Initiation of Highly Active Antiretroviral Therapy
Open Access
- 15 July 2001
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 75 (14), 6508-6516
- https://doi.org/10.1128/jvi.75.14.6508-6516.2001
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.This publication has 13 references indexed in Scilit:
- Functionally Inert HIV-Specific Cytotoxic T Lymphocytes Do Not Play a Major Role in Chronically Infected Adults and ChildrenThe Journal of Experimental Medicine, 2000
- Putative Immunodominant Human Immunodeficiency Virus-Specific CD8+T-Cell Responses Cannot Be Predicted by Major Histocompatibility Complex Class I HaplotypeJournal of Virology, 2000
- Immune control of HIV-1 after early treatment of acute infectionNature, 2000
- Dynamics of HIV-Specific CD8+ T Lymphocytes with Changes in Viral LoadThe Journal of Immunology, 2000
- Anti-Human Immunodeficiency Virus Type 1 (HIV-1) CD8+T-Lymphocyte Reactivity during Combination Antiretroviral Therapy in HIV-1-Infected Patients with Advanced ImmunodeficiencyJournal of Virology, 2000
- HIV-1–specific immune responses in subjects who temporarily contain virus replication after discontinuation of highly active antiretroviral therapyJCI Insight, 1999
- HIV-1-specific CD4+ T cells are detectable in most individuals with active HIV-1 infection, but decline with prolonged viral suppressionNature Medicine, 1999
- Incidence of Immune Recovery Vitritis in Cytomegalovirus Retinitis Patients following Institution of Successful Highly Active Antiretroviral TherapyThe Journal of Infectious Diseases, 1999
- The Effect of Commencing Combination Antiretroviral Therapy Soon after Human Immunodeficiency Virus Type 1 Infection on Viral Replication and Antiviral Immune ResponsesThe Journal of Infectious Diseases, 1999
- Immune Recovery Vitritis Associated With Inactive Cytomegalovirus RetinitisAmerican Journal of Ophthalmology, 1998