title: IL28B CC genotype is associated with higher all-cause mortality in antiretroviral-treated HIV-infected patients.
abstract: Il28B single nucleotide polymorphisms were found to influence interferon λ expression, resulting in changes in hepatitis C virus (HCV)-RNA serum levels as well as the HIV-RNA set point prior to combined antiretroviral therapy (cART). To date, there is limited information on the influence of this polymorphism on survival in HIV-infected, treatment-naïve, and antiretroviral-treated patients. Longitudinal data from 484 patients diagnosed with HIV infection (including 406 on cART) were analyzed to investigate the association between Il28B rs 1979860 variants and all-cause mortality. Kaplan-Meyer and Cox models were used to calculate the hazard ratio associated with IL28B genotypes predictive of a greater likelihood of survival for patients prior to the introduction of cART and for patients on cART. The IL28B genotype frequencies were 41.7% (n=202) for CC, 46.5% (n=225) for CT, and 11.7% (n=57) for TT patients. The CC variant was associated with higher mortality (46 cases, 22.8%) compared to other genotypes [n=31 (13.8%) and n=7 (12.3%) for CT and TT, respectively, p=0.02]. IL28 genotypes did not influence the survival probability prior to treatment initiation (HR 1.04, 95% CI: 0.84-1.24, p=0.68). In antiretroviral-treated patients, after adjustment for gender, baseline CD4 count, CDC category at HIV diagnosis, and age (multivariate HR 1.75, 95% CI: 1.20-2.30, p=0.047), the CC genotype was associated with a decreased probability of survival when compared to the non-CC genotype (univariate HR 1.8, 95% CI: 1.28-2.34, p=0.029). IL28B rs12979860 genotypes influence mortality risk in HIV-infected, antiretroviral-treated patients. The effect may be related to higher baseline plasma HIV viremia and possibly altered immune reconstitution associated with interferon λ expression.
authors.affiliation: Department of Infectious Diseases and Hepatology, Pomeranian Medical University, Szczecin, Poland. mparczewski@yahoo.co.uk
authors.forename: Miłosz
authors.initials: M
authors.lastname: Parczewski
authors.forename: Dorota
authors.initials: D
authors.lastname: Bander
authors.forename: Magdalena
authors.initials: M
authors.lastname: Leszczyszyn-Pynka
authors.forename: Anna
authors.initials: A
authors.lastname: Urbańska
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Socha
authors.forename: Anna
authors.initials: A
authors.lastname: Boroń-Kaczmarska
mesh_terms: D000328:Adult; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000276:immunology* / Q000401:mortality*; D016174:Hepacivirus; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics* / Q000276:immunology*; D008137:Longitudinal Studies; D008297:Male; D009026:Mortality; D020641:Polymorphism, Single Nucleotide; D016019:Survival Analysis; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda