While the new treatments for hepatitis C have improved dramatically in terms of cure rates and side effects (and pharmaceutical companies bottom-line), there are still patients who do not respond, especially those with genotype 3. A recent study (Hepatology 2015; 61: 56-65) has provided some information into why this is happening.
A division of the FDA looked into five sofosbuvir (SOF) trials and performed sequencing to characterize potential resistance-associated substitutions.
- Nonstructural protein 5B (NS5B) substitutions, L159F and V321A, emerged in 2.2%-4.4% of subjects who failed SOF treatment.
- Baseline substitutions in 316 were associated with a reduced response in HCV genotype 1b subjects.
- This study identified only 11 patients with genotype 3 with potentially relevant substitutions.
Bottomline: In the vast majority of patients, no resistance-associated substitution could be identified, indicating that we have a lot to learn why some patients are not responding.
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