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

Abstract

Introduction: 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). Methods: 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. Results: 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). Conclusion: 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.

HCV spontaneous clearers showed low senescence profile in people living with HIV under long ART

“…DNA was extracted from PBMCs using the DNA Purification System Kit (Promega Wizard). We performed the quantification of replicative senescence by monochromatic multiplex real‐time quantitative PCR (MMqPCR) as previously described 25 . To normalize and control the number of telomere copies/sample we used the single‐copy gene (β‐globin).…”

Relative telomere length impact on mortality of COVID‐19: Sex differences

“…RTL quantification was carried out by monochromatic multiplex real‐time quantitative PCR (MMqPCR) assay as previously described 9 (see Appendix Data 1 for extended information).…”

Decrypting biological hallmarks of aging in people with HIV

“…Although ART regimens, including those containing tenofovir, could impact telomere length by affecting telomerase activity [38], progressive telomere length shortening is associated with delaying ART initiation [39]. Furthermore, shorter telomere length in PLWH is associated with higher levels of inflammatory biomarkers, excessive CD8 þ T cell activation, and increased incidence and risk of multiple age-related comorbid diseases among PLWH on ART [40][41][42].…”