Ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination resulted in sustained virologic response (SVR) rates of 93-97% for both treatment naïve and experienced genotype 1 HCV-infected patients with or without cirrhosis. As more patients are treated with this regimen, a population of treatment failures is emerging. We describe 13 patients who failed LDV/SOF despite having an undetectable viral load at the end of therapy.
This observational cohort study was conducted on patients who failed LDV/SOF therapy at the Mount Sinai Medical Center during the interval between March and September 2015. Data were collected on age, sex, viral genotype, presence or absence of cirrhosis, prior history of hepatocellular carcinoma (HCC), co-infection with HIV, previous therapy regimen, and duration of LDV/SOF.
Thirteen patients failed treatment, and only one had HIV co-infection (Table). Ten (77%) were male with a mean age of 60 years (range 34-69). Most (n=11) had genotype 1 HCV, six had 1a, four had 1b, one had 1l. Eight (62%) had liver cirrhosis; among them, five had a history of hepatocellular carcinoma (HCC) that was treated by liver transplantation (n=2), by chemoembolization (n=2), or resection (n=1). Six of the 13 (46%) had a history of prior HCV treatment failure. All prior regimens were IFN/RBV based; one included telaprevir. Regarding LDV/SOF treatment, 11 (85%) had 12 weeks of therapy, one had 24 weeks, and one had eight weeks. Six relapsed by post treatment week (PTW) four, and all relapsed by PTW 13. NS3 and NS5A resistance panels have been sent on all patients and will be reported.
In clinical practice, although LDV/SOF treatment failures are rare, they are growing in number. Liver cirrhosis and HCC may be risk factors. Information about patients who fail treatment may identify groups of patients who would benefit from a longer duration of therapy or a triple-drug regimen.