Responder Interferon λ Genotypes Are Associated With Higher Risk of Liver Fibrosis in HIV–Hepatitis C Virus Coinfection

BACKGROUND Liver fibrosis progresses faster in individuals coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Interferon λ3 (IFN-λ3) has both antiviral and proinflammatory properties. Genotypes at IFNL single-nucleotide proteins (SNPs; rs12979860CC and rs8099917TT) are linked to higher HCV clearance, potentially via rs8103142. We examined the relationship between IFN-λ genotypes and significant liver fibrosis in HIV-HCV coinfection. METHODS From the prospective Canadian Co-infection Cohort (n = 1423), HCV RNA-positive participants in whom IFN-λ genotypes were detected and who were free of fibrosis, end-stage liver disease, and chronic hepatitis B at baseline (n = 485) were included. Time to significant fibrosis (defined as an aspartate transaminase level to platelet count ratio index [APRI] of ≥1.5) by IFN-λ genotypes was analyzed using Cox proportional hazards, with adjustment for age, sex, ethnicity, alcohol use, CD4(+) T-cell count, HCV genotype, γ-glutamyl transferase level, and baseline APRI. Haplotype analysis was performed, with adjustment for ethnicity. RESULTS A total of 125 participants developed fibrosis over 1595 person-years (7.84 cases/100 person-years; 95% confidence interval [CI], 6.58-9.34 cases/100 person-years). Each genotype was associated with an increased fibrosis risk, with adjusted hazard ratios of 1.37 (95% CI, .94-2.02) for rs12979860CC, 1.34 (95% CI, .91-1.97) for rs8103142TT, and 1.79 (95% CI, 1.24-2.57) for rs8099917TT. Haplotype TCT was also linked with a higher risk (hazard ratio, 1.14 [95% CI, .73-1.77]). CONCLUSIONS IFN-λ SNPs rs12979860, rs8099917, and rs81013142 were individually linked to higher rates of fibrosis in individuals with HIV-HCV coinfection. IFN-λ genotypes may be useful to target HCV treatments to people who are at higher risk of liver disease.