Persistent Abnormalities in Peripheral Blood Dendritic Cells and Monocytes from HIV-1-Positive Patients After 1 Year of Antiretroviral Therapy

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Abstract
Summary: Antiretroviral therapy (ART) has led to marked decreases in morbidity and mortality rates among HIV-1-positive patients; however, immune recovery is not complete. Although dendritic cells (DCs) were shown to be involved in HIV-1 pathogenesis, few studies have investigated the effect of ART on DCs. We have analyzed the effect of ART on numerical distribution, expression of chemokine receptors, and ex vivo production of inflammatory cytokines by peripheral blood (PB) monocytes and DCs in a cohort of chronically infected HIV-1-positive patients. Patients were tested before therapy and at weeks +2, +4, +8, +12, and +52 after starting ART. Our results show an incomplete T-cell immune reconstitution in chronically infected patients who had undetectable plasma viremia while taking ART for 1 year. This was associated with persistent abnormalities at week +52 of ART, corresponding to increased numbers of CD16+ DCs and monocytes, as well as altered expression of CXC chemokine receptors, in the form of increased CXCR1 expression on monocytes and decreased reactivity for CXCR2 and/or CXCR4 on myeloid and plasmacytoid DCs. In addition, an abnormally high spontaneous ex vivo secretion of inflammatory cytokines by CD16+ DCs and monocytes was still detected after 1 year of ART. These abnormalities were especially pronounced in patients with less than 200 CD4+ T cells/μL, which could be related to the persistence of undetected viral replication and sustained immune activation.