Hepatitis C viral load, genotype 3 and interleukin-28B CC genotype predict mortality in HIV and hepatitis C-coinfected individuals

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Abstract
Objective: We hypothesized that hepatitis C virus (HCV) load and genotype may influence all-cause mortality in HIV-HCV-coinfected individuals. Design and methods: Observational prospective cohort study. Mortality rates were compared in a time-updated multivariate Poisson regression analysis. Results: We included 264 consecutive HIV-HCV-coinfected individuals. During 1143 person years at risk (PYR) 118 individuals died [overall mortality rate 10 (95% confidence interval; 8, 12)/100 PYR]. In multivariate analysis, a 1 log increase in HCV viral load was associated with a 30% higher mortality risk [adjusted mortality rate ratio (aMRR): 1.30 (1.10,1.54)] when adjusted for sex, age, HIV exposure group, CD4 cell count, HIV RNA, HCV genotype and interleukin (IL)-28B genotype. Further, HCV genotype 3 vs. 1 [aMRR: 1.83 (1.12, 2.98)] and HIV RNA [aMRR: 3.14 (1.37,7.17) for undetectable vs. just detectable HIV RNA] were independent predictors of mortality, whereas a higher CD4 cell count was associated with a 41% reduction in mortality rate per 50 cell increase between 0 and 200 cells/μl [aMRR: 0.59 (0.48, 0.72)] and a 10% reduction for increases above 200 cells/μl [aMRR: 0.90 (0.82–0.98)]. IL28B) CC genotype was associated with 54% higher mortality risk [aMRR: 1.54 (0.89, 3.82] compared to TT genotype. Conclusion: High-HCV viral load, HCV genotype 3 and IL28B genotype CC had a significant influence on the risk of all-cause mortality among individuals coinfected with HIV-1. This may have consequences for the management of HIV-HCV-coinfected individuals.