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AIDS. 2013 Nov 13;27(17):2715-24. doi: 10.1097/01.aids.0000432459.36970.a9.

Variations at multiple genes improve interleukin 28B genotype predictive capacity for response to therapy against hepatitis C infection.

Author information

1
aUnit of Infectious Diseases and Microbiology, Hospital Universitario de Valme bInstituto de Biomedicina de Sevilla (IBiS), Seville cImmunogenetics Unit, Faculty of Sciences, Universidad de Jaén, Jaen dUnit of Infectious Diseases, Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Cordoba eDepartment of Infectious Diseases, Hospital Carlos III, Madrid fUnit of Infectious Diseases, Hospital Juan Ramón Jiménez. Huelva, Spain.

Abstract

OBJECTIVE:

To identify genetic factors that predict sustained virological response (SVR) to pegylated interferon (Peg-IFN)/ribavirin (RBV) in HIV/hepatitis C virus (HCV) genotype 1 or 4-coinfected patients and that enhance the predictive capacity of IL28B genotype in this population.

DESIGN:

Prospective cohort study.

SETTING:

Five tertiary care centers in Spain.

PATIENTS:

Two hundred and five HIV/HCV genotype 1 or 4-coinfected patients who received a complete course of Peg-IFN/RBV for 48 weeks.

MAIN OUTCOME MEASURES:

All individuals were genotyped for 144 single-nucleotide polymorphisms (SNPs).

RESULTS:

One hundred and sixty-two (79%) patients bore HCV genotype 1. Overall SVR was achieved by 73 (36%) individuals. SNPs at the following genes were associated with SVR: IL28B, low-density lipoprotein receptor (LDLR), transforming growth factor β (TGF-β), aquaporine 2 (AQP-2), very-low-density lipoprotein receptor, Sp110 nuclear body protein, interferon alpha/beta receptor 1, 2'-5'-oligoadenylate synthase 1 and apolipoprotein B. There was a strong synergy between SNPs at IL28B, TGF-β and AQP-2 genes: the number of patients reaching SVR with all three favorable genotypes versus unfavorable genotypes were 22 (78.6%) versus 1 (7.1%) (P = 2.1 × 10). HCV baseline viral load, IL28B, TGF-β, AQP-2 and LDLR haplotypes were independently associated with SVR.

CONCLUSION:

A number of genetic factors modify the predictive capacity of IL28B genotype. These can be used to identify HCV genotype 1 or 4-infected patients with a very high or a very low probability to respond to bitherapy with Peg-IFN/RBV. Predictive models based on these factors could be helpful to tailor direct acting antiviral-based therapy.

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