BACKGROUND: Treatment with Peg-interferon and ribavirin (PEG-IFN/RBV) for HIV patients co-infected with hepatitis C virus (HCV) genotype 1 has suboptimal rates of response. Viral kinetics has emerged as one of the best prognostic factors of treatment outcome.
METHODS: Twenty HIV/HCV genotype 1 co-infected patients in treatment with PEG-IFN/RBV, had blood drawn at baseline, 24h, 4, 12, 24, 48, and 72weeks. HCV-RNA levels were evaluated at each time point. ROC curves were used to evaluate the log(10) HCV-RNA decay at 24h that exhibits the best predictive value of achieving response. Genomic characterization of HCV NS5A at both interferon sensitivity-determining region (ISDR) and protein-kinase binding (PKRBD) domains were performed in order to evaluate its heterogeneity and association with 24h HCV-RNA decay and SVR.
RESULTS: Non-responder patients exhibited a mean of 0.7log(10) (SD 0.74log(10)) HCV-RNA decay at 24h, whereas responder-patients presented 1.6log(10) (SD 0.28log(10)), p=0.04. A reduction in HCV viral load from baseline to 24h of <1.4 had a negative predictive value for achieving SVR of 100% and a positive predictive value of 50%. HCV genotype 1 isolates from patients with a decrease of HCV-RNA at 24h >1.4log(10), exhibited 3.1(SD 1.5) amino acids substitutions in ISDR and 4.8(SD 2.3) in PKRBD regions and 1.6(SD 0.7) and 2.4(SD1.3), respectively, in those patients presenting lower reduction in HCV-RNA.
CONCLUSIONS: HIV/HCV genotype 1 co-infected patients with a decrease in HCV-VL at 24h >1.4 log(10) are more likely to achieve SVR when treated with PEG-IFN/RBV than those with lower levels of HCV-RNA decay. Along with other host-related and viral-related prognostic factors in HIV/HCV co-infected patients, this very early time point of evaluation could be of relevance in the management of HCV-specific treatment.