Background: Expression of CD38 on T-lymphocytes has been used as a marker of immune activation in HIV infection and has prognostic value on disease progression, independently of CD4⁺ counts. However, little is known about the differential expression of this molecule in naive versus memory subsets of both CD4 and CD8 T-cells, as well as the effect of antiretroviral therapy on this parameter.

Objective: To quantify the expression of CD38 on naive and memory subsets of CD4 and CD8 T-cells in chronic HIV infection, and the impact of antiretroviral therapy.

Methods: We included160 untreated HIV⁺ patients (pts) and 30 age-matched seronegative controls in the study; 25 patients initiated HAART and were followed for 6 months (mos). CD38 molecules were quantified on different subsets of CD4 and CD8 T-cells by flow cytometry.

Results: CD38 was significantly elevated in memory CD4 and CD8 cells in HIV⁺ pts when compared to seronegative controls (5048 ±4164 vs 1109 ±351 and 7600 ±5604 vs 670 ±471 molecules/cell for CD4 memory and CD8 memory subsets, respectively, p < 0.001). Activation in naive cells was slightly increased in CD8 cells, but was not significantly different from controls. In univariate analyses, a strong direct correlation was found between plasma viremia and level of activation in all subsets, being higher for memory subsets (r = 0.73 and 0.72 for CD4 and CD8 memory cells, p < 0.0001). CD4 counts showed an inverse correlation with these subsets (r = -0.49 and -0.48 for CD4 and CD8 memory cells, p < 0.01). In multivariate analysis, the level of activation of CD4 memory cells was the strongest predictor of both plasma viremia and CD4 counts. With the reduction in plasma viremia induced by HAART, the level of activation declined significantly in memory CD4 and CD8 T-cell subsets, although it was not completely normalized after 6 mos of therapy. In contrast, activation was completely normalized by HAART in naive CD8 cells.

Conclusions: HIV infection induces different levels of activation in different subsets of T-cells, being CD8 memory cells the most activated, followed by CD4 memory cells. In contrast, CD4 naive cells remain unchanged. However, the strongest predictor of plasma viremia and CD4 counts was the level of activation in CD4 memory cells. Only the activation in CD8 naive cells was completely restored after 6 mos of successful HAART. Quantitative analysis of CD38 might be a more precise and sensitive tool to measure immune activation in HIV infection.