Gamma-Delta T-Cell Phenotype and Function in DAA-Treated HIV-HCV Co-Infected and HCV-Mono-Infected Subjects
Valeria Bono; Camilla Tincati; Lorena Van Den Bogaart; Elvira Stefania Cannizzo; Roberta Rovito; Matteo Augello; Anna De Bona; Antonella D’Arminio Monforte; Laura Milazzo; Giulia Marchetti
HIV-HCV co-infected subjects are at risk of liver fibrosis which may be linked to immune imbalances. Direct-acting antivirals (DAAs) represent the mainstay of HCV treatment in co-infected individuals, yet their effects on immune cell populations playing a role in fibrogenesis is unknown. We assessed &gamma:&delta: T-cell phenotype and function, Treg and Th17 frequencies, as well as &gamma:-globulins and B-cell activation in 47 HIV-HCV co-infected and 35 HCV mono-infected individuals prior to and following DAA treatment (SVR12). &Gamma:&delta: T-cell activation decreased in both groups yet persisted at higher levels in the HIV-HCV co-infected subjects. No differences were registered in terms of &gamma:&delta:T-cell function. Of note, the V&delta:2/Th17 ratio, inversely linked to liver damage, increased significantly in the two groups upon treatment, yet a negative correlation between the V&delta:2/Th17 ratio and liver function enzymes was found in the co-infected subjects alone. B-cell activation and &gamma:-globulin levels decreased in both settings, yet B-cell activation remained higher in the HIV-HCV co-infected individuals. In HIV-HCV co-infected and HCV mono-infected participants, the effect of DAA was limited to &gamma:&delta: T- and B-cell activation as well as &gamma:-globulin concentrations and the V&delta:2/Th17 ratio, with no changes in &gamma:&delta: T-cell function and Treg frequencies. Importantly, &gamma:&delta: T- and B-cell activation remained at higher levels in the co-infected individuals than in those with HCV mono-infection alone. The persistence of such alterations within these cell subsets may be associated with the risk of hepatic and extrahepatic complications.
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