Factors associated with resolution and progression of HIV/hepatitis C virus infection.

Coinfection with hepatitis C virus (HCV) is common in human immunodeficiency virus (HIV)-infected individuals as a result of shared routes of transmission, and this coinfection represents a special challenge. For HIV-HCV-coinfected individuals, the burden of disease is largely related to their HCV diseases, including a faster progression to liver fibrosis, cirrhosis and liver-related deaths. In the present thesis we investigated factors associated with spontaneous resolution and progression of HIV-HCV coinfection. In study I, we identified the study cohort of 327 individuals with HIV-HCV coinfection and a rate of spontaneous HCV resolution of 23%. We showed that female sex, coinfection with hepatitis B virus and individuals exposed through injecting drug use (IDU) or homosexual contact (MSM) had an increased rate of spontaneous HCV resolution. We speculate that differences in resolution rate may be caused by immunological memory induced by repeatedly being exposed to low-dose inoculum of HCV. In study II, we found three single-nucleotide-polymorphisms (SNPs) in the interleukin 28B (IL28B) gene associated with spontaneous HCV resolution in 208 Europeans of Caucasian origin with HIV-HCV coinfection. Further, we showed that the IL28B CC genotype favourable of HCV resolution was associated with a higher HCV viral load (VL) than non-CC genotypes. These results may indicate an influence of IL28B in viral control. In study III, we conducted a survival analysis in the 264 HIV-HCV-coinfected individuals with chronic infection. We showed in a time-updated Poisson regression that HCV VL, HCV genotype 3 and IL28B CC genotype were predictors of increased mortality. This may indicate a need for closer observation in HIV-HCV-coinfected individuals with HCV genotype 3 and maybe even initiation of antiviral therapy.