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

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.