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

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 ill 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. (C) 1998 Elsevier Science B.V. All rights reserved.