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

Antiviral Res. 1998 Oct;39(3):163-73. doi: 10.1016/s0166-3542(98)00035-7.

Abstract

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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-HIV Agents / therapeutic use*
  • Antigens, CD / metabolism
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / drug effects*
  • 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 / drug effects*
  • Humans
  • Immunologic Memory
  • Immunophenotyping
  • Indinavir / therapeutic use*
  • Lamivudine / therapeutic use*
  • Lymphocyte Activation
  • Statistics, Nonparametric
  • T-Lymphocyte Subsets / drug effects
  • Viral Load
  • Zidovudine / therapeutic use*

Substances

  • Anti-HIV Agents
  • Antigens, CD
  • HIV Protease Inhibitors
  • Lamivudine
  • Zidovudine
  • Indinavir