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

Abstract

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 were 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 week 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.