Comparison of CD4⁺ T-cell subset distribution in chronically infected HIV⁺ patients with various CD4 nadir counts

Infection with HIV-1 causes CD4⁺ T-cell dysfunction, including unresponsiveness to antigenic stimuli. To understand the mechanism of virally induced T-cell dysfunction, we investigated changes occurred in functional CD4⁺ T-cell subsets in the peripheral CD4⁺ T-cell pool in chronically infected aviremic individuals treated with antiretroviral therapy. We phenotypically defined CD4⁺ T-cell subsets by surface markers and determined the frequency of each subset by flow cytometry. A substantially low naïve and elevated effector subsets were observed in chronically infected patients with nadir CD4 counts <100 cells/μl. The skewed distribution persisted in these patients even after their CD4 counts increased, and the subset imbalance was still observed in all four subsets after years of successful antiretroviral therapy. They also showed a limited recovery of CD4⁺ T-cell counts compared to those who maintained at least 250 CD4⁺ T cells/μl after 3-11 years of successful treatment since CD4 nadir time points. The difference was pronounced in the absolute numbers of naïve and T_EM cells. Our results suggested a significant and prolonged impact of nadir CD4 counts on the balanced distribution of the functional CD4⁺ T-cell subsets and may explain partially why antiretroviral therapy needs to be initiated while patients' CD4 counts remain relatively high.