ITPA deficiency and ribavirin level are still predictive of anaemia in HCV-HIV-coinfected patients receiving ribavirin combined with a first-generation DAA (ANRS HC27 study).

Background: We aimed to determine the impact of inosine triphosphatase (ITPA) deficiency on ribavirin (RBV)-induced anaemia in HIV-HCV-coinfected patients receiving a triple therapy including the haematotoxic direct-acting antiviral agent boceprevir (BOC).& para;& para;Methods: Patients of the ANRS HC27 BocepreVlH study were genotyped for two ITPA single nucleotide polymorphisms involved in ITPA deficiency. RBV trough concentration (C-trough) was determined at week (W)4 and W8. Impact of ITPA deficiency on anaemia, RBV C-trough,C- response and haematotoxicity (grade 3/4 anaemia, erythropoietin [EPO] use, RBV dose reduction or transfusion between day RAO and W8) was evaluated. Impact of RBV C-trough, on anaemia was also studied.& para;& para;Results: Among the 63 genotyped patients, 33% had a predicted ITPA deficiency. ITPA deficiency was associated with a lower haemoglobin (Hb) decline both at W4 (-1.0 g.dl versus -2.1 g/dl, P=0.02) and W8 (-2.7 g/dl versus -4.1 g/dl; P=0.05). None of the patients with ITPA deficiency received EPO between D0-W8 versus 26% of patients without ITPA deficiency (P=0.01). RBV C-trough was associated with Hb decrease both at W4 and W8 and an RBV C-trough cutoff value of 2 mu g/ml was significantly associated with a W4 Hb decline >2 g/dl. Haematotoxicity was significantly associated with a lower W4 Hb level (P=0.017), absence of ITPA deficiency (P=0.018) and higher RBV C-trough (P=0.012). ITPA deficiency, W4 RBV C-trough and gender were independent predictors of anaemia at W4. ITPA deficiency was not associated with virological response.& para;& para;Conclusions: ITPA deficiency and RBV C-trough are still predictive of RBV-induced anaemia in HIV-HCV-coinfected patients treated with RBV combined with a first-generation direct antiviral agent.