Dynamics of cellular senescence markers after HCV elimination spontaneously or by DAAs in people living with HIV

Abstract

Background: We identified that acute or chronic Hepatitis C (HCV) infection in people living with HIV (PLWHIV) results in different senescence profiles. However, variations in these profiles after HCV elimination, spontaneously or with direct-acting antivirals (DAAs), remain unclear. Methods: Longitudinal observational study (48 weeks) in 70 PLWHIV: 23 PLWHIV with active HCV-chronic infection (CHC) before and after HCV eradication with DAAs, 12 PLWHIV who spontaneously clarify the HCV (SC), and 35 controls (HIV). Oxidative stress was quantified at DNA, lipid, protein, and nitrate levels, as well as the antioxidant capacity and glutathione enzyme. The replicative senescence was evaluated by relative telomere length measurement by PCR and twenty-six factors related to Senescence-Associated Secretory Phenotype (SASP) were characterized by Luminex. Differences in senescence markers was evaluated by generalized linear models. Results: During follow-up, the SC group achieved a significant improvement in glutathione enzyme and lipid peroxidation. The secretion of SASP markers increased but was still lower than that of the HIV group. Overall, the CHC group reduced the levels of oxidative stress and SASP markers to levels like those of the HIV group. No significant differences in telomere shortening were observed between groups. Conclusions: As the time since spontaneous resolution of HCV infection increased, patients had an improved senescence profile compared to the HIV group. Elimination of chronic HCV infection by DAAs led to a partial improvement of the senescent profile by restoring oxidative stress levels. However, although some SASP markers reached levels like those of the HIV group, others remained altered.