Association of ITPA gene polymorphisms and the risk of 1 ribavirin - induced anemia in HIV / HCV co - infected 2 patients on HCV combination therapy

42 Background 43 Polymorphisms of the ITPA gene have been associated with anemia during 44 combination therapy in HCV mono-infected patients. Our aim was to confirm this 45 association in HIV/HCV co-infected patients 46 Methods 47 In this prospective, observational study, 73 HIV/HCV co-infected patients treated with 48 Peg-IFN plus RBV were enrolled. Two SNPs within or adjacent to ITPA gene (rs1127354 49 and rs7270101) were genotyped. The associations between the ITPA genotype and 50 anemia or treatment outcome were examined. 51 Results 52 Fifty-nine patients (80.8%) had CC at rs 1127354 whereas 14 (19.2%) had a CA/AA 53 ITPA genotype. Percent decreases from baseline hemoglobin level were significantly 54 greater in patients with CC than in those with CA/AA genotype at week 4 (P = 0.0003), 55 week 12 (P < 0.0001), week 36 (P = 0.0102), but not at the end of treatment. RBV dose 56 reduction was more often needed in patients with CC than in those with CA/AA 57 genotype (OR = 11.81; 95%CI: 1.45-256.17, P = 0.0039) as was erythropoietin therapy 58 (OR = 8.28; 95%CI: 1.04-371.12, P = 0.0057). Risk factors independently associated 59 with percent hemoglobin nadir decrease were: RBV dose reduction (OR = 11.72; 95CI: 60 6.82-16.63, P < 0.001), baseline hemoglobin (OR = 1.69; 95%CI: 0.23-3.15, P = 0.024), 61 and BMI (OR = -0.7, 95%CI: -1.43-0.03, P = 0.061). ITPA polymorphism was not an 62 independent predictor of sustained virological response. 63 Conclusions 64 Polymorphisms at rs 1127354 in the ITPA gene influence hemoglobin levels during 65 combination HCV therapy and the need for RBV dose reduction and erythropoietin 66 use in HIV/HCV co-infected patients. 67 68 Word count: 250 69 70 on O cber 2, 2017 by gest httpaac.asm .rg/ D ow nladed fom