Association of ITPA gene polymorphisms and the risk of ribavirin-induced anemia in HIV/hepatitis C virus (HCV)-coinfected patients receiving HCV combination therapy

Pere Domingo, Josep M. Guardiola, Juliana Salazar, Ferran Torres, M. Gracia Mateo, Cristina Pacho, M. Del Mar Gutierrez, Karuna Lamarca, Angels Fontanet, Jordi Martin, Jessica Muñoz, Francesc Vidal, Montserrat Baiget

Research output: Contribution to journalArticleResearchpeer-review

18 Citations (Scopus)

Abstract

Polymorphisms of the ITPA gene have been associated with anemia during combination therapy in hepatitis C virus (HCV)- monoinfected patients. Our aim was to confirm this association in HIV/HCV-coinfected patients. In this prospective, observational study, 73 HIV/HCV-coinfected patients treated with pegylated interferon plus ribavirin (RBV) were enrolled. Two single nucleotide polymorphisms within or adjacent to the ITPA gene (rs1127354 and rs7270101) were genotyped. The associations between the ITPA genotype and anemia or treatment outcome were examined. Fifty-nine patients (80.8%) had CC at rs1127354, whereas 14 (19.2%) had a CA/AA ITPA genotype. Percent decreases from baseline hemoglobin level were significantly greater in patients with the CC genotype than in those with the CA/AA genotype at week 4 (P = 0.0003), week 12 (P < 0.0001), and week 36 (P = 0.0102) but not at the end of treatment. RBV dose reduction was more often needed in patients with the CC genotype than in those with the CA/AA genotype (odds ratio [OR] = 11.81; 95% confidence interval [CI] = 1.45 to 256.17; P = 0.0039), as was erythropoietin therapy (OR = 8.28; 95% CI = 1.04 to 371.12; P = 0.0057). Risk factors independently associated with percent hemoglobin nadir decrease were RBV dose reduction (OR = 11.72; 95% CI = 6.82 to 16.63; P < 0.001), baseline hemoglobin (OR = 1.69; 95% CI = 0.23 to 3.15; P = 0.024), and body mass index (OR = -0.7; 95% CI = -1.43 to 0.03; P = 0.061). ITPA polymorphism was not an independent predictor of sustained virological response. Polymorphisms at rs1127354 in the ITPA gene influence hemoglobin levels during combination HCV therapy and the need for RBV dose reduction and erythropoietin use in HIV/HCV-coinfected patients. Copyright © 2012, American Society for Microbiology. All Rights Reserved.
Original languageEnglish
Pages (from-to)2987-2993
JournalAntimicrobial Agents and Chemotherapy
Volume56
Issue number6
DOIs
Publication statusPublished - 1 Jun 2012

Fingerprint Dive into the research topics of 'Association of ITPA gene polymorphisms and the risk of ribavirin-induced anemia in HIV/hepatitis C virus (HCV)-coinfected patients receiving HCV combination therapy'. Together they form a unique fingerprint.

Cite this