Highly active antiretroviral therapy results in a decrease in CD8 + T cell activation and preferential reconstitution of the peripheral CD4 + T cell population with memory rather than naive cells

• Published in: Antiviral research 1998-10, Vol.39 (3), p.163-173
• Main Authors: Evans, Thomas G, Bonnez, William, Soucier, Harold R, Fitzgerald, Theresa, Gibbons, David C, Reichman, Richard C
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antigens, CD - metabolism; Antiviral agents; Biological and medical sciences; CD38; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes - drug effects; CD45RA; CD62L; CD8-Positive T-Lymphocytes - drug effects; Drug Therapy, Combination; Flow Cytometry; HIV Infections - drug therapy; HIV Infections - immunology; HIV Protease Inhibitors - therapeutic use; HIV-1; HIV-1 - drug effects; Humans; Immunologic Memory; Immunophenotyping; Indinavir - therapeutic use; Lamivudine - therapeutic use; Lymphocyte Activation; Medical sciences; Pharmacology. Drug treatments; Statistics, Nonparametric; T-Lymphocyte Subsets - drug effects; Viral Load; Zidovudine - therapeutic use
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/S0166-3542(98)00035-7

Objective: Highly active antiretroviral therapy (HAART) can produce marked increases in peripheral blood CD4 + T cells and decreases in HIV plasma RNA copy numbers. However, it is not clear whether these absolute changes will be accompanied by a recovery in the known naive CD4 + T cell depletion or a decrease in the marked CD8 + T cell activation. Design: Twenty-nine patients were enrolled in studies of either nucleoside therapy alone or nucleoside therapy combined with a protease inhibitor (zidovudine+lamivudine+indinavir). One hundred and ninety-one examinations were carried out at three baseline time points and during 40 weeks of follow-up to evaluate the effect of HAART on CD4 + memory/naive phenotype and CD8 + T cell activation. Methods: CD4 + and CD8 + T cell number, CD62L/CD45RA expression on CD4 + T cells and CD38 expression on CD8 + T cells were measured by three-color flow cytometry. Results: Most protease inhibitor treated patients had a significant rise in CD4 + numbers. The marked rise in the CD4 + T cells seen in individuals in this study was not accompanied over a 40-week period by a change in the abnormally low CD4 + naive compartment, and thus was almost completely of memory phenotype. The CD38 expression on CD8 + cells fell during treatment, and decreased to a greater degree than the comparable rise in CD4 + T cell counts. This decrease continued in many patients after the CD4 + T cell rise or viral load decline had plateaued. Conclusion: HAART results in changes in activation to a greater extent than absolute changes in CD4 + T cell numbers, but is not accompanied by an increase in naive CD4 + T cells. Measurements of CD4 + T cell numbers alone may not allow appropriate interpretation of immune activation or immune competence in patients receiving those drugs.