Baseline drug resistance mutations are detectable by population sequencing in hepatitis C genes NS3 and NS5A but not NS5B in acute and chronic hepatitis C/HIV co-infected patients

Background: There is a continuing epidemic of acute hepatitis C (HCV) in HIV positive MSM. The current standard of care is treatment with pegylated- interferon plus ribavirin (pIFN/RBV) in the early phase of disease (<12 months) which is associated with favourable outcomes. If chronicity develops, newer direct acting antiviral drugs (DAAs) may be used with pIFN/RBV which target HCV NS3, NS5A and NS5B. Recent data suggest that shorter courses of pIFN/ RBV and an NS3 protease inhibitor can be used in acute genotype (gt) 1 HCV infection. However, HCV resistance associated mutations (RAMs) at baseline may be associated with poorer outcomes to therapy. We sought to quantify these in acute and chronic HIV/HCV co-infected patients. Methods: Samples were obtained from 3 groups of HIV/HCV co-infected patients: (1) acute (2) chronic treatment-na € ıve (3) chronic treatment-experienced (pIFN/RBV). Plasma viral RNA was extracted and genotyped by population sequencing of HCV genomic regions (sites of known RAMs) ie: amino acids 1-181 of the HCV NS3 protease for gt1, amino acids 1-213 of domain I of NS5A and amino acids 219-347 of NS5B. Results: Baseline RAMs were detected in all 3 groups in NS3 and NS5A (table). Conclusion: RAMs that may confer resistance to HCV DAAs are frequently encountered as baseline polymorphisms in both acute and chronic infection. Resistant variants exist as the dominant species (by population sequencing) and minority resistant variants may be detectable by ultra-deep sequencing. The implications of this remain to be fully established but, in some cases, pre- treatment sequencing may be indicated to limit treatment failures