Association between IL28B rs12979860 genotypes and susceptibility to HCV and/or HIV infection in Caucasian intravenous drug users M. Pauskar1, R. Avi1, E. Kallas1, E-L Jõgeda1, T. Karki1, A. Uusküla2, D. Des Jarlais3, I. Lutsar1, K. Huik 1Universtiy of Tartu, Department of Microbiology, Tartu, Estonia; 2University of Tartu, Department of Public Health, Tartu, Estonia 3Beth Israel Medical Center, New York, USA Background The CC genotype (rs12979860) of IL28B (interferon-λ3) gene has been associated with treatment-induced HCV elimination and the clearance of HCV without treatment. In-vitro studies have demonstrated antiviral effect of interferon-λ on HIV replication. In addition, Machmach et al (2012) suggest that common host mechanisms such as IL28B rs12979860 are involved in the spontaneous control of both HIV and HCV infections. Aim To evaluate associations between IL28B genotypes and susceptibility to HCV and/or HIV infection. The IL28B rs12979860 TT genotype frequency was (Figure 1): a) similar among HCV- IDUs, HCV+ IDUs and blood donors; b) different between HIV- IDUs, HIV+ IDUs and blood donors. a) Figure 1. The IL28B rs12979860 TT genotype frequency distribution among: a) HCV- IDUs, HCV+ IDUs and donors b) HIV- IDUs, HIV+ IDUs and donors. Material and Methods A total of 344 Caucasian intravenous drug users (IDUs) were recruited; 50% were HIV, 89% HCV and 77% HBV seropositive. The control group consisting of 495 blood donors were tested negative for all three viruses. IL28B rs12979860 genotyping was carried out by using TaqMan Allelic Discrimination Assay. Results The distribution of IL28B genotypes in blood donors and IDUs, were as follows: CC (45.5% and 44.5%), CT (45.1% and 43.3%) and TT (9.5% and 12.2%). P=0.030 P=0.024 b) 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 100% 90% 80% TT nonTT 70% 60% TT 50% 40% nonTT 30% 20% 10% 0% HCV- HCV+ Donors N=38 N=306 N=495 HIV- HIV+ Donors N=172 N=172 N=495 In univariate analysis, IDUs with TT genotype had higher odds of being HIV seropositive, compared to IDUs not having TT genotype. After adjustment to HCV and HBV serostatus, and the duration of intravenous drug use the association did not remain significant (Tabel 1). Tabel 1. Associations between IL28B TT genotype and susceptibility to HIV infection Comparison TT vs. non-TT Outcome: HIV positivity; OR (95% CI) Unadjusted Adjusted* 2.19 (1.11 – 4.33) 1.84 (0.89 – 3.80) *Adjusted to HCV, HBV and the duration of intravenous drug use Conclusions TerVE Acknowledgment: The study was supported by the Target Financing of Estonian Ministry of Education and Research (SF0180004s12 and IUT34-24 ) and by European Union through the European Regional Development Fund and by the Archimedes Foundation. IL28B rs12979860 TT genotype might be associated with enhanced acquisition of HIV infection which could be mediated by antiviral activity of interferon λ. [email protected]
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