Telaprevir enhances ribavirin-induced anaemia through renal function impairment.

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.