Normalization of CD4+ cell numbers and reduced levels of memory CD8+ cells in blood and tonsillar tissue after highly active antiretroviral therapy in early HIV type-1 infection

Antiretroviral therapy increases the number of both CD4(+) and CD8(+) T cells in the blood of HIV-1-positive patients with advanced disease. In the present study, we have examined the kinetics of CD4(+) and CD8(+) T cell restoration in blood and lymphoid tissue in asymptomatic HIV-1-positive individuals with high CD4(+) cell counts during highly active antiretroviral treatment. Tonsillar biopsies and blood samples were collected at baseline and at regular intervals during the following 48 weeks and from HIV-1-negative controls. Mononuclear cells from blood and tonsils mere phenotyped and quantified by three-color flow cytometry, After 48 weeks of therapy, blood CD4(+) cell counts in the HIV-1-infected group were comparable to those found in uninfected controls. Naive CD4(+) T cells in blood increased during the initial 2 weeks in parallel with reduced plasma viremia, Both naive and memory CD4(+) T cells in blood reached normal numbers by meek 48, whereas the CD4(+) naive/memory cell ratio in tonsils was,within normal range throughout the study. The level of memory CD8(+) T cells in blood declined during the first 8 weeks in parallel with a reduction in the tonsillar memory CD8(+) T cells. Naive CD8(+) T cells in the blood increased after 4 weeks, while the level of naive CD8(+) T cells in tonsils remained unaltered. Our data indicate that in the early stages of HIV-1 infection antiretroviral therapy normalizes CD4(+) cell counts and causes a decrease in the level of memory CD8(+) cells in blood and lymphoid tissue, suggesting reduced CD8(+) cell turnover in response to reduced viral replication.