Failure with HCV DAA regimen in a high volume treatment center under real life conditions

Background: HCV DAA therapies yielded SVR12 rates of more than 90% in randomized clinical trials. Given this remarkable efficacy, understanding factors associated with treatment failures in real-world clincal practice remains challenging due to the relatively small number of patients who do not achieve SVR.

Aim: To examine a large number of patients from an experienced high volume treatment center of ID physicians and hepatologists selecting patients conjointly for HCV treatment to assess the characteristics of patients who failed available DAA therapies since licensing in mid 2014.

Methods: Data were collected retrospectively from a single treatment center using a centralized electronic data base. All HCV patients that started DAA treatment since June 2014 and finished treatment (fu12) until March 2016 were included (n = 935).

Results: Overall, SVR rate from this very heterogenous patient population was 92%. Of the patients that did not achieve SVR, 4% discontinued treatment, lacked adherence, or were lost to follow-up. 4% were virologic failures, mostly relapsers (n = 44), viral breakthrough n = 2. In the virological failures, age, race, viral load, genotype, or HIV coinfection were not associated with treatment failure. Associated with failure was advanced cirrhosis with platelets less than 100,000/ml plus prior treatment failure and GT3. Timing of antiviral therapy showed a trend to a greater risk of failure finishing therapy end of 2014 compared to end of 2015. Furthermore, there was a trend towards failure in cirrhotic patients who developed an HCC that was detected over the following nine months after relapse.

Conclusions: Overall failure rate in real world HCV patients of different genotypes and various states of liver disease from a high volume treatment center was 8% with 4% diagnosed as showing relapse and 4% treatment discontinuation, lack of adherence or lost to follow up. SVR rates were high across treatment regimen. Patient characteristics with advanced cirrhosis with thrombocytopenia and prior treatment failure and GT3 represented the most difficult to treat patients. Patient selection might further reduce the number of treatment discontinuation and lost to follow up. We detected only a very limited number of reinfections so far in PWIDs.