Telomere Length Increase in HIV/HCV-Coinfected Patients with Cirrhosis after HCV Eradication with Direct-Acting Antivirals.

Abstract

Human immunodeficiency virus (HIV) infection and cirrhosis are associated with a senescent phenotype that decreases telomere length. We evaluated the impact of hepatitis C virus (HCV) elimination on telomere length in patients with advanced HCV-related cirrhosis after sustained virological response (SVR), with all-oral direct-acting antiviral agents (DAAs). Prospective study of 60 HIV/HCV-coinfected and 30 HCV-monoinfected patients with advanced HCV cirrhosis (liver decompensation or liver stiffness measurement (LSM) ≥ 25 kPa, hepatic liver pressure gradient (HVPG) ≥ 10 mmHg, or Child-Pugh-Turcotte (CPT) ≥ 7). The relative telomere length (RTL) was quantified by real-time multiplex PCR (MMqPCR) on peripheral blood mononuclear cells at baseline and 48 weeks after HCV treatment. Generalized linear models (GLMs) adjusted for the most relevant clinical and epidemiological variables and mixed GLMs were used. In comparison with HCV-monoinfected patients, HIV/HCV-coinfected patients were younger (p < 0.001), had lower body mass index (BMI) (p = 0.002), and had been exposed less frequently to interferons (p = 0.011). In addition, they were more frequently men (p = 0.011), smokers (p = 0.005), prior intravenous drug users (IVDUs) (p < 0.001), and alcohol abusers (p = 0.005). RTL was significantly lower in HIV/HCV-coinfected patients than in HCV-monoinfected patients, both at baseline (p < 0.001), and at the end of follow-up (p = 0.032). A significant RTL increase over time was found only for HIV/HCV-coinfected patients (p < 0.001), especially in those patients with compensated cirrhosis (p < 0.001). HCV eradication with all-oral DAAs was associated with an increase in telomere length in HIV/HCV-coinfected patients with advanced cirrhosis, particularly in compensated patients. This finding suggests that HCV clearance may have implications in age-related conditions in this population group.We want to particularly acknowledge the support of the HIV BioBank, which is integrated in the Spanish AIDS Research Network, and all collaborating centers for the generous contribution of clinical samples for the present work (see Appendix A). The HIV BioBank is supported by the Instituto de Salud Carlos III and the Spanish Health Ministry (grant nos. RD06/0006/0035, RD12/0017/0037, and RD16/0025/0019) as part of the Plan Nacional R + D + I, and is co-financed by the ISCIII Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER). The Spanish HIV/AIDS Research Network (RIS) Cohort (CoRIS) is funded by the Instituto de Salud Carlos III through the Red Temática de Investigación Cooperativa en SIDA (RIS C03/173, RD12/0017/0018, and RD16/0002/0006) as part of the Plan Nacional R + D + I, and is co-financed by the ISCIII Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER). Furthermore, this study would not have been possible without the collaboration of all the patients, as well as the medical and nursery staff and data managers who have taken part in the project.S