Section 57
Chapter 56,849

Variants in the ITPA gene protect against ribavirin-induced hemolytic anemia in HIV/HCV-coinfected patients with all HCV genotypes

Naggie, S.; Rallon, N.I.; Benito, J.é M.; Morello, J.; Rodriguez-Novoa, S.; Clark, P.J.; Thompson, A.J.; Shianna, K.V.; Vispo, E.; McHutchison, J.G.; Goldstein, D.B.; Soriano, V.

Journal of Infectious Diseases 205(3): 376-383


ISSN/ISBN: 1537-6613
PMID: 22158703
DOI: 10.1093/infdis/jir754
Accession: 056848283

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A recent genome-wide association study reported a strong association with a single-nucleotide polymorphism (SNP) in the inosine triphosphate (ITPA) gene and hemolytic anemia in patients infected with hepatitis C virus (HCV) receiving pegylated interferon and ribavirin. We investigate these polymorphisms in a cohort of human immunodeficiency virus (HIV)/HCV-coinfected patients. DNA was available for 161 patients with validated outcomes. We analyzed the association between the variants and week 4 hemoglobin reduction. Anemia over the course of therapy, ribavirin (RBV) dose reduction, serum RBV level, and rapid virological response (RVR) and sustained virological response (SVR) were also investigated. Using a candidate gene approach, ITPA variants rs1127354 and rs7270101 were tested using the ABI TaqMan kit. Multivariable models were used to identify predictors of anemia. A significant minority (33%) of patients were predicted to have reduced ITPase activity. The minor allele of each variant was associated with protection against week 4 anemia. In multivariable models only the genetic variants, creatinine, and zidovudine exposure remained significant. ITPase deficiency was not associated with RBV-dose reduction, RVR, or SVR. This study confirms that polymorphisms in the ITPA gene are associated with protection from RBV-induced anemia in HIV/HCV-coinfected patients but not improved clinical outcomes.

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