title: Telaprevir enhances ribavirin-induced anaemia through renal function impairment.
abstract: BACKGROUND
  Alterations in renal function have been described with telaprevir (TVR). We examined the relationship between ribavirin (RBV) trough concentration (C), estimated glomerular filtration rate (eGFR) and severe anaemia, before and after TVR introduction in HIV-HCV-coinfected patients included in ANRS HC26 TelapreVIH study.
  
  
  METHODS
  69 HIV-HCV genotype-1 coinfected patients received 4 weeks of pegylated interferon (PEG-IFN)-α2a/RBV, followed by 12 weeks of TVR/PEG-IFN/RBV, then 32 to 56 weeks of PEG-IFN/RBV. RBV C was determined at week (W)4, W8 and W20/24. eGFR was estimated by the Modification of the Diet in Renal Disease (MDRD) equation. Severe anaemia was defined as haemoglobin <70 g/l, RBV dose reduction, prescription of erythropoietin or blood transfusion.
  
  
  RESULTS
  67 patients were analysed. eGFR remained normal between baseline (97.9 ml/min) and W4 (103.4 ml/min), declined to 86.3 ml/min at W8 (P<0.0001), stabilized until W16 and increased back to baseline level at W20 (98.4 ml/min). RBV C increased from 1.88 mg/l at W4 to 2.88 mg/l at W8 (P<0.0001), then decreased to 2.73 mg/l at week 20/24 (P=0.015). An inverse correlation was observed between W8 eGFR and W8 RBV C (r2=0.429; P=0.0005). RBV C≥3 mg/l was observed in 12% of patients at W4, 45% at W8 (P<0.0001) and 38% at W20/24 (P=0.0005). Severe anaemia was observed in 23.9% of patients at W4 and 45.3% at W8. RBV C≥3 mg/l at W8 (OR 7.7 [95% CI 2.2, 27.4]) and baseline haemoglobin <150 g/l (OR 6.4 [1.7, 23.8]) were independently associated with W8 severe anaemia.
  
  
  CONCLUSIONS
  Association of TVR to PEG-IFN/RBV was associated with a decrease in eGFR and increase in RBV C, leading to severe anaemia in 45% of patients.
authors.affiliation: Croix-Rousse Hospital, Hospices Civils de Lyon, Lyon, France. laurent.cotte@chu-lyon.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Cotte
authors.forename: Aurélie
authors.initials: A
authors.lastname: Barrail-Tran
authors.forename: Corine
authors.initials: C
authors.lastname: Vincent
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Valantin
authors.forename: Isabelle
authors.initials: I
authors.lastname: Fournier
authors.forename: Karine
authors.initials: K
authors.lastname: Lacombe
authors.forename: Stéphane
authors.initials: S
authors.lastname: Chevaliez
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Aboulker
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Taburet
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
mesh_terms: D000740:Anemia / Q000139:chemically induced*; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects* / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D051437:Renal Insufficiency / Q000139:chemically induced*; D012254:Ribavirin / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C100416:peginterferon alfa-2a