IFNL4-rs12979860 CC genotype predisposes to accelerated terminal exhaustion and senescence in HIV/HCV-chronic infection.

PURPOSE: rs12979860 polymorphism of the lambda 4 interferon (IFNL4) gene has been related with Hepatitis C Virus (HCV) spontaneous clearance (CC genotype favourable versus CT/TT). The implications of this polymorphism over chronic-HCV disease are unknown, particularly during Human Immunodeficiency virus (HIV) coinfection.

METHODS

Observational study in 118 people with HIV (PWH): 45 with HCV-chronic infection (CHC); 38 who spontaneously clear HCV (SC) and 35 never infected by HCV (HIV). Expression of surface markers was evaluated in CD4+ and CD8+ memory T cells by flow cytometry, and plasma markers were quantified by Luminex or ELISA.

RESULTS

CHC individuals with CC genotype (CHC-CC) showed higher expression of markers suggestive of senescence (PD1/CD57) and activation markers (CD38/CD25) in CD8 + T-cell subpopulations, compared to CT/TT carriers. Similarly, significantly higher expression was observed in CD4+ and CD8+ T cells in CHC-CC than SC-CC and HIV-CC controls. Regarding plasma markers, CHC-CC group had higher levels of 19 plasma immune biomarkers compared to CT/TT carriers, and 16 relative to SC-CC, including pro- and anti-inflammatory cytokines, while oxidative stress slightly diminished in CHC-CC individuals.

CONCLUSIONS

CC-carriage may result in premature cellular activation and senescence or impaired functionality during HCV chronic infection in PWH, which may be masked by their maintained plasma immune homeostasis during clinical monitoring.