TY - JOUR

T1 - Hepatitis C viral load, genotype 3 and interleukin-28B CC genotype predict mortality in HIV and hepatitis C-coinfected individuals

AU - Clausen, Louise Nygaard

AU - Astvad, Karen

AU - Ladelund, Steen

AU - Larsen, Mette Vang

AU - Schønning, Kristian

AU - Benfield, Thomas

PY - 2012/7/31

Y1 - 2012/7/31

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - CD4 Lymphocyte Count

KW - Female

KW - HIV

KW - HIV Infections/mortality

KW - Hepacivirus/genetics

KW - Hepatitis C/genetics

KW - Humans

KW - Interleukins/genetics

KW - Male

KW - Middle Aged

KW - Prognosis

KW - Prospective Studies

KW - RNA, Viral/blood

KW - Risk Factors

KW - Viral Load

U2 - 10.1097/QAD.0b013e3283553581

DO - 10.1097/QAD.0b013e3283553581

M3 - Journal article

C2 - 22555162

VL - 26

SP - 1509

EP - 1516

JO - AIDS

JF - AIDS

SN - 1350-2840

IS - 12

ER -