HCV clearance by direct antiviral agents is associated with decreased expression of interferon stimulated genes but not with the size of the inducible HIV reservoir

A. URIOSTE; A. CZERNIKIER; A. PALETTA; F. REMES LENICOV; A. OSEGUEDA; M.L POLO; A. SISTO; G. TURK; Y. GHIGLIONE; N. LAUFER

Mar del Plata

Congreso; LXIX Reunión Científica de la Sociedad Argentina de Inmunología; 2022

Sociedad Argentina de Inmunología

Purpose: Previous results from our group indicated that HCV clearance by direct antiviral agents (DAAs) in HCV/HIV coinfected individuals results in higher HIV RNA expression. Here, we extended this finding and evaluated the impact of HCV clearance on the size of the inducible HIV reservoir, the magnitude of the HIV-specific T-cell response and the expression of interferon induced genes (ISG). Methods: prospective longitudinal study. 22 HIV/HCV coinfected individuals were enrolled (12 with METAVIR fibrosis scale compatible with F4 and 10 with F0/F1). All individuals were on successful antiretroviral therapy and began HCV treatment with DAAs. Peripheral blood samples (PBMC) were obtained before DAAs (BSL), at the end of treatment (EOT) and 12 months post-treatment (12MPT). ISGs, OAS-1, Mx-1 and IRF-7 were analyzed by qRT-PCR, HIV specific response was evaluated by flow cytometry after stimulation with Nef and Gag peptides. Specific cells were identified by intracellular cytokine staining. Tat/Rev induced limiting dilution assay (TILDA) was used to quantify the inducible HIV reservoir. Results: A no significant increase on the HIV reservoir between BSL and 12MPT wasMPT was observed for F4 patients, whereas a decrease was observed for F0. No differences were found in the magnitude of the HIV-specific T-cell response. However, a significant decline in the expression of ISG OAS-1 and Mx-1 was found between BSL and 12 MPT samples (OAS-1 [mean±SD: 0,12±0,23 vs 0,04±0,06(–ΔCt)2, p=0,0313] and Mx-1 [0.65±1.09 vs 0.06±0.05(–ΔCt)2, p=0,0156]). Conclusions: After HCV clearance ISG showed a lower cell expression. This might be due to the elimination of HCV-antigen chronic stimulation. Nevertheless, we could not find a modification on HIV parameters within the time-frame evaluated, such as the inducible reservoir and the HIV-specific response secondary to this reduction in the ISG pathway. Larger time of follow up and number of individuals could help to further evaluate these parameters