Decay Kinetics of Human Immunodeficiency Virus-Specific CD8+ T Cells in Peripheral Blood after Initiation of Highly Active Antiretroviral Therapy
AUTOR(ES)
Casazza, Joseph P.
FONTE
American Society for Microbiology
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=114374Documentos Relacionados
- Decay Kinetics of Human Immunodeficiency Virus-Specific Effector Cytotoxic T Lymphocytes after Combination Antiretroviral Therapy
- Human Immunodeficiency Virus-Specific CD8+ T Cells in Human Breast Milk
- Kinetics of Virus-Specific CD8+ T Cells and the Control of Human Immunodeficiency Virus Infection
- Defective Human Immunodeficiency Virus-Specific CD8+ T-Cell Polyfunctionality, Proliferation, and Cytotoxicity Are Not Restored by Antiretroviral Therapy▿
- Human Immunodeficiency Virus-Specific CD8+ T-Cell Responses Do Not Predict Viral Growth and Clearance Rates during Structured Intermittent Antiretroviral Therapy