| Autor: |
Wang GP; University of Florida, Gainesville, USA. gary.wang@medicine.ufl.edu.; North Florida/South Georgia Veterans Health System, Gainesville, USA. gary.wang@medicine.ufl.edu., Terrault N; University of California, San Francisco, San Francisco, USA., Reeves JD; Monogram Biosciences, South San Francisco, USA., Liu L; University of Florida, Gainesville, USA., Li E; University of Florida, Gainesville, USA., Zhao L; University of Florida, Gainesville, USA., Lim JK; Yale University School of Medicine, New Haven, USA., Morelli G; University of Florida, Gainesville, USA., Kuo A; Virginia Mason Medical Center, Seattle, USA., Levitsky J; Northwestern University Feinberg School of Medicine, Chicago, USA., Sherman KE; University of Cincinnati, Cincinnati, USA., Frazier LM; Liver Wellness Center, Little Rock, USA., Ramani A; Columbia Memorial Hospital (Mountainview Medical Center), Hudson, USA., Peter J; University of Florida, Gainesville, USA., Akuskevich L; University of North Carolina, Chapel Hill, United States., Fried MW; University of North Carolina, Chapel Hill, United States., Nelson DR; University of Florida, Gainesville, USA. |
| Abstrakt: |
Baseline resistance-associated substitutions (RASs) have variable impacts in clinical trials but their prevalence and impact in real-world patients remains unclear. We performed baseline resistance testing using a commercial assay (10% cutoff) for 486 patients treated with LDV/SOF or SMV/SOF, with or without ribavirin, in the multi-center, observational HCV-TARGET cohort. Linkage of RASs was evaluated in selected samples using a novel quantitative single variant sequencing assay. Our results showed that the prevalence of NS3, NS5A, NS5B RASs was 45%, 13%, and 8%, respectively, and 10% of patients harbored RASs in 2 or more drug classes. Baseline LDV RASs in GT1a, TE, and cirrhosis LDV/SOF subgroup was associated with 2-4% lower SVR12 rates. SMV RASs was associated with lower SVR12 rates in GT1a, treatment-experienced, cirrhotics SMV/SOF subgroup. Pooled analysis of all patients with baseline RASs revealed that SVR12 was 100% (19/19) in patients treated for longer than 98 days but was 87% (81/93) in patients treated for shorter than 98 days. These results demonstrate that RASs prevalence and their impact in real world practice are in general agreement with registration trials, and suggest that longer treatment duration may overcome the negative impact of baseline RASs on SVR12 rates in clinical practice. |
