rs7270101

This study examined ITPA gene polymorphisms (rs1127354 and rs7270101) in 121 patients with HIV/HCV coinfection (n=63) and HCV monoinfection (n=58) treated with pegIFN/RBV. ITPA deficiency was found protective against hemoglobin reduction >3 g/dl (P=0.020 at week 4 in coinfected patients) and was associated with rapid virologic response at week 4 (P=0.017) in HIV/HCV coinfected patients, but did not improve sustained virologic response.

This study examined ITPA gene polymorphisms (rs1127354) and their influence on hemoglobin decreases during triple therapy with pegylated interferon, ribavirin, and telaprevir in 61 Japanese patients with hepatitis C virus genotype 1. Patients with the CC genotype at rs1127354 experienced significantly greater hemoglobin reductions (Δ-3.5 ± 1.1 g/dL at week 4, P=0.001) compared to CA/AA genotypes, required more RBV dose reductions during the first 12 weeks (52% vs 65% of target dose, P=0.039), and had higher risk for severe anemia (OR=36.8 for hemoglobin <11 g/dL). SVR rates were comparable between genotypes (71% vs 67%, P=0.736), demonstrating that with careful monitoring and dose adjustment, effective HCV treatment can be achieved despite genetic predisposition to RBV-induced anemia.

Two functional ITPA gene variants (rs1127354 and rs7270101) were strongly protective against ribavirin-induced hemolytic anemia in 238 HCV genotype 2/3 patients treated with pegylated interferon and ribavirin (P=10^-6 and P=10^-7 respectively; combined P=10^-11). Despite protection from anemia, ITPA variants did not decrease the need for ribavirin dose reduction or improve sustained virological response.

This is a special issue of the Italian medical journal BeAdfiles (September 2012) dedicated to genetic conditioning in HIV and hepatitis virus infections. It reviews the major genetic polymorphisms that influence disease progression, treatment response, and drug toxicity in HIV and chronic hepatitis B and C infections, with particular emphasis on IL28B polymorphisms (rs809917 and others) predicting HCV treatment response to interferon-alpha and ribavirin therapy, and ITPA gene variants protecting against ribavirin-induced anemia. The issue also covers pharmacogenetic markers (CYP2B6, ABCB1, HLA-B*5701) and their clinical applications in antiretroviral therapy.