Relationship between CD38 expression on peripheral blood T‐cells and monocytes, and response to antiretroviral therapy: A one‐year longitudinal study of a cohort of chronically infected ART‐naive HIV‐1+ patients

Abstract

HIV-1 infection has been associated with high expression of CD38 on peripheral blood (PB) CD8+ and CD4+ T-cells, which has been related with poor prognosis in untreated HIV-1+ patients. In turn, CD38 expression on PB monocytes from HIV-1+ individuals and its behavior after starting antiretroviral therapy (ART) have been poorly studied. CD38 expression on PB CD8+ and CD4+ T-lymphocytes and monocytes was prospectively analyzed in 30 ART-naive HIV-1+ patients, using a quantitative multiparameter flow cytometry approach. Patients were tested prior to therapy, and at weeks +2, +4, +8, +12, and +52 after ART. Prior to ART, CD38 expression was significantly increased on PB CD8+ and CD4+ T-cells and monocytes; despite a significant decrease after ART, CD38 expression remained abnormally high on PB CD8+ T-cells and monocytes, even after one year of therapy, in the absence of detectable plasma viral load. The ART-induced early changes on CD38 expression by PB T-cells and monocytes differed among the cell subsets analyzed and patient groups, probably reflecting an interaction between the direct effects of therapy and a redistribution of the PB compartments of T-cells and monocytes. Hierarchical clustering analysis showed that the overall pattern of changes in CD38 expression observed early after starting ART was predictive of a better response to therapy, not only for PB CD8+ T-cells, but also for CD4+ T-cells and monocytes. Accordingly, those HIV-1+ patients, who experienced a more pronounced increase in CD38 expression on both PB CD4+ T-cells and monocytes after 2 weeks of ART, showed a more rapid viral clearance, which might reflect decreased HIV-1 replication in lymph nodes and other tissues, and a partial restoration of hematopoiesis. Combined quantitative measurement of CD38 expression on PB monocytes, and CD8+ and CD4+ T-cells is a more useful tool for monitoring HIV-1+ patients under ART, rather than quantitation of CD38 expression on PB CD8+ T-lymphocytes alone.