Retreatment with sofosbuvir, ledipasvir, and add-on ribavirin for patients who failed daclatasvir and asunaprevir combination therapy.
BACKGROUND
The optimal retreatment regimen for patients with hepatitis C virus (HCV) infection who failed interferon-free, direct-acting antiviral (DAA) therapy is undetermined. In this study, we aimed to evaluate the efficacy and safety of 12-week retreatment with ledipasvir (LDV) and sofosbuvir (SOF) with add-on ribavirin (RBV) for patients who previously failed to respond to HCV-NS5A inhibitor, daclatasvir (DCV), and HCV-NS3 inhibitor, asunaprevir (ASV), therapy.


METHODS
This multicenter, prospective study enrolled 15 patients with genotype-1 HCV infection who failed DCV/ASV combination therapy. They were retreated with SOF, LDV, and RBV for 12 weeks and underwent physical examinations and blood tests at baseline, during treatment, and after therapy. At baseline and relapse, NS3/NS5A and NS5B resistance-associated variants (RAVs) were evaluated.


RESULTS
Of the 15 enrolled patients, 73.3% (11/15), 86.7% (13/15), and 0% (0/15) had RAVs in NS3 D168A/V/T/E, NS5A L31I/M/F/V plus Y93H, and NS5B S282T, respectively. Overall, 86.7% (13/15) of patients achieved a sustained viral response, and all patients completed therapy. No patients experienced severe adverse events. Two patients who failed to respond to SOF, LDV, and RBV combination therapy were elderly women, had the IL28B non-TT genotype, and NS5A RAVs in L31I/Y93H or NS5A A92 K at baseline.


CONCLUSIONS
This study revealed that SOF, LDV, and RBV combination therapy was effective and well-tolerated for patients with genotype-1 HCV infection who failed DCV and ASV combination therapy. Thus, RBV added to DAA therapy for difficult-to-treat patients might improve treatment outcomes.
['Suda|Goki|G|', 'Ogawa|Koji|K|', 'Yamamoto|Yoshiya|Y|', 'Katagiri|Masaki|M|', 'Furuya|Ken|K|', 'Kumagai|Kenichi|K|', 'Konno|Jun|J|', 'Kimura|Megumi|M|', 'Kawagishi|Naoki|N|', 'Ohara|Masatsugu|M|', 'Umemura|Machiko|M|', 'Ito|Jun|J|', 'Izumi|Takaaki|T|', 'Nakai|Masato|M|', 'Sho|Takuya|T|', 'Natsuizaka|Mitsuteru|M|', 'Morikawa|Kenichi|K|', 'Tsubota|Akihito|A|', 'Shimada|Noritomo|N|', 'Iio|Etsuko|E|', 'Tanaka|Yasuhito|Y|', 'Sakamoto|Naoya|N|', '|||']
D000368:Aged D000998:Antiviral Agents D001562:Benzimidazoles D002219:Carbamates D004359:Drug Therapy, Combination D005260:Female D005449:Fluorenes D005838:Genotype D016174:Hepacivirus D019698:Hepatitis C, Chronic D006801:Humans D007093:Imidazoles D007546:Isoquinolines D008297:Male D008875:Middle Aged D011446:Prospective Studies D011759:Pyrrolidines D019233:Retreatment D012254:Ribavirin D000069474:Sofosbuvir D013449:Sulfonamides D016896:Treatment Outcome D014633:Valine
Retreatment Sofosbuvir Daclatasvir Hepatitis C virus Direct-acting antivirals