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Modulation of monocyte activation and function during direct antiviral agents treatment in HIV coinfected patients.

Abstract

BACKGROUND: The activation phenotype and functional changes in monocyte subsets during HCV elimination in HIV/HCV-coinfected patients were evaluated.METHODS: 22 HIV/HCV-coinfected patients on suppressive combination antiretroviral treatment (cART) achieving HCV elimination after direct-acting antivirals (DAAs) therapy and 10 HIV-monoinfected patients were included. Activation phenotype (10 markers) and polyfunctionality (intracellular IL1alpha, IL1beta, IL6, IL8, TNFalpha and IL10 production) in three monocyte subsets (classical, intermediate and nonclassical) were evaluated by flow cytometry before and at the end of treatment. Cell-associated HIV-DNA levels were assayed by droplet digital PCR.RESULTS: After HCV clearance there was a significant increase in classical monocytes and a decrease in intermediate and nonclassical monocytes levels. The activation markers, CD49d, CD40, CX3CR1, decreased after treatment in the monocyte subsets reaching the levels of HIV-monoinfected patients. After LPS stimulation, although polyfunctionality significantly decreased in intermediate and nonclassical monocytes, some combinations such as IL1alpha-IL1beta-IL6+IL8-TNFalpha-IL10- were remarkably increased at the end of treatment compared to the control group. Cell-associated HIV-DNA levels correlated with activation markers before but not after treatment.CONCLUSIONS: HCV clearance after DAAs treatment in patients on cART exerts an anti-inflammatory profile in monocyte subsets, activation phenotypes and polyfunctionality. However, there is not a complete normalization compared with HIV-monoinfected patients.

Authors: De Pablo-Bernal RS, Jimenez-Leon MR, Tarancon-Diez L, Gutierrez-Valencia A, Serna-Gallego A, Trujillo-Rodriguez M, Alvarez-Rios AI, Milanes-Guisado Y, Espinosa N, Roca-Oporto C, Viciana P, Lopez-Cortes LF, Ruiz-Mateos E,
Journal: Antimicrob. Agents Chemother.; 2020 Jun 22 . doi:10.1128/AAC.00773-20
Year: 2020
PubMed: PMID: 32571815 (Go to PubMed)