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Title

Modulation of Monocyte Activation and Function during Direct Antiviral Agent Treatment in Patients Coinfected with HIV and Hepatitis C Virus

AuthorsPablo-Bernal, Rebeca de; Jiménez-León, María Reyes; Tarancón-Díez, Laura; Gutiérrez Valencia, Alicia; Serna, Ana CSIC ORCID; Trujillo-Rodríguez, María; Álvarez-Ríos, Ana Isabel; Milanés-Guisado, Yusnelkis; Espinosa, Nuria; Roca-Oporto, Cristina; Viciana, Pompeyo; López-Cortés, Luis F. CSIC; Ruiz-Mateos, Ezequiel
KeywordsDAAs
HCV
HIV
Activation
Cell-associated DNA: Inflammation
Monocyte: Polyfunctionality
Reservoir
Issue Date20-Aug-2020
PublisherAmerican Society for Microbiology
CitationAntimicrobial Agents and Chemotherapy 64: 00773-20 (2020)
AbstractThe activation phenotypes and functional changes in monocyte subsets during hepatitis C virus (HCV) elimination in HIV/HCV-coinfected patients were evaluated. Twenty-two HIV/HCV-coinfected patients on suppressive combination antiretroviral treatment (cART) achieving HCV elimination after direct-acting antiviral (DAA) therapy and 10 HIV-monoinfected patients were included. The activation phenotype (10 markers) and polyfunctionality (intracellular interleukin-1α [IL-1α], IL-1β, IL-6, IL-8, tumor necrosis factor alpha [TNF-α], and IL-10 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. After HCV clearance, there was a significant increase in classical monocyte and decreases in intermediate and nonclassical monocyte levels. The levels of the activation markers CD49d, CD40, and CX3CR1 were decreased after treatment in the monocyte subsets, reaching the levels in HIV-monoinfected patients. After lipopolysaccharide (LPS) stimulation, although polyfunctionality significantly decreased in intermediate and nonclassical monocytes, some combinations, such as the IL-1α− (IL-1α-negative) IL-1β− IL-6+ (IL-6-producing) IL-8− TNF-α− IL-10− combination, 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. HCV clearance after DAA treatment in patients on cART exerts an anti-inflammatory profile on monocyte subsets, activation phenotypes, and polyfunctionality. However, there is not a complete normalization compared with HIV-monoinfected patients.
Publisher version (URL)http://ddoi.org/10.1128/AAC.00773-20
URIhttp://hdl.handle.net/10261/230136
Identifiersdoi: 10.1128/AAC.00773-20
issn: 0066-4804
e-issn: 1098-6596
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