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.


METHODS
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.


CONCLUSIONS
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.
Evans
T G
TG
Infectious Diseases Unit, University of Rochester, NY, USA.
Bonnez
W
W
Soucier
H R
HR
Fitzgerald
T
T
Gibbons
D C
DC
Reichman
R C
RC
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015703:Antigens, CD / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects*; D004359:Drug Therapy, Combination; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D019469:Indinavir / Q000627:therapeutic use*; D019259:Lamivudine / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D018709:Statistics, Nonparametric; D016176:T-Lymphocyte Subsets / Q000187:drug effects; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D015703:Antigens, CD; D017320:HIV Protease Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019469:Indinavir