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).

ABSTRACT

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). METHODS: Patients of the ANRS HC27 BocepreVIH study were genotyped for two ITPA single nucleotide polymorphisms involved in ITPA deficiency. RBV trough concentration (Ctrough) was determined at week (W)4 and W8. Impact of ITPA deficiency on anaemia, RBV Ctrough, response and haematotoxicity (grade 3/4 anaemia, erythropoietin [EPO] use, RBV dose reduction or transfusion between day [D]0 and W8) was evaluated. Impact of RBV Ctrough on anaemia was also studied. 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 Ctrough was associated with Hb decrease both at W4 and W8 and an RBV Ctrough cutoff value of 2 µg/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 Ctrough (P=0.012). ITPA deficiency, W4 RBV Ctrough and gender were independent predictors of anaemia at W4. ITPA deficiency was not associated with virological response. CONCLUSIONS: ITPA deficiency and RBV Ctrough are still predictive of RBV-induced anaemia in HIV-HCV-coinfected patients treated with RBV combined with a first-generation direct antiviral agent.