Mitochondrial genotoxicity of hepatitis c treatment among people who inject drugs

Mélusine Durand, Nicolas Nagot, Quynh Bach Thi Nhu, Roselyne Vallo, Linh Le Thi Thuy, Huong Thi Duong, Binh Nguyen Thanh, Delphine Rapoud, Catherine Quillet, Hong Thi Tran, Laurent Michel, Thanh Nham Thi Tuyet, Oanh Khuat Thi Hai, Vinh Vu Hai, Jonathan Feelemyer, Philippe Vande Perre, Don Des Jarlais, Khue Pham Minh, Didier Laureillard, Jean Pierre Molès

Research output: Contribution to journalArticlepeer-review

Abstract

Antiviral nucleoside analogues (ANA) are newly used therapeutics acting against the hepatitis C virus (HCV). This class of drug is well known to exhibit toxicity on mitochondrial DNA (mtDNA). People who inject drugs (PWID) are particularly affected by HCV infection and cumu-lated mitotoxic drug exposure from HIV treatments (antiretrovirals, ARV) and other illicit drugs. This study aims to explore the impact of direct-acting antiviral (DAA) treatments on mtDNA among PWID. A total of 470 actively injecting heroin users were included. We used quantitative PCR on whole blood to determine the mitochondrial copy number per cell (MCN) and the proportion of mitochondrial DNA deletion (MDD). These parameters were assessed before and after DAA treat-ment. MDD was significantly increased after HCV treatment, while MCN did not differ. MDD was even greater when subjects were cotreated with ARV. In multivariate analysis, we identified that poly-exposure to DAA and daily heroin injection or regular consumption of methamphetamines were positively associated with high MCN loss while DAA and ARV treatments or methadone use were identified as risk factors for having mtDNA deletion. These observations deserve attention since they were previously associated with premature cell ageing or cell transformation and there-fore call for a long-term follow-up.

Original languageEnglish (US)
Article number4824
JournalJournal of Clinical Medicine
Volume10
Issue number21
DOIs
StatePublished - Nov 1 2021

Keywords

  • Drug users
  • Genotoxicity
  • HCV treatment
  • Mitochondria

ASJC Scopus subject areas

  • Medicine(all)

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