studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 731A
were 71% of interferon-ineligible/intolerant patients and 89%
of prior non-response patients. Non-virological response was
evaluated in 583 patients, and the rates were 3%. The higher
levels of NS5A-Y93 mutant affected the higher rates of non-virological
response, significantly. Especially, in patients of IL28B
rs8099917 non TT with NS5A-Y93 mutant levels 16 on
CES-D) recorded in 44%. Average medication adherence was
97%. Among patients who used drugs in the past month and
year, adherence was 92% and 96%, respectively. Medication
adherence in those who drank alcohol in past year was 97%.
Nonadherence was due to missing doses (67%) and potential
double-dosing (33%). Clinic attendance to scheduled visits was
95% (range: 87% - 100%). All 32 patients (100%) completed
the full duration of 12 weeks of therapy. At 12-week EOT visit,
97% had HCV RNA below the level of quantitation. Conclusion:
Rates of medication adherence, clinic attendance, and
persistence are extremely high in patients with SUDs/AUDs.
These data provide no justification for withholding treatment
from these patients due to adherence concerns. Clinicians
and patients need to be aware of accidental double-dosing.
Research is needed to determine the extent to which financial
incentives are needed to optimize adherence and to identify a
new adherence threshold that may jeopardize viral cure.
Disclosures:
The following authors have nothing to disclose: Donna M. Evon, Angela Edwards,
Becky Straub, Christopher B. Hurt, Harsha Thirumurthy, David Wohl
1064
Frequent Emergences of Rare RAVs Showing Extreme
Resistance to NS5A Inhibitors during Dual Oral Threpy
with Daclatasvir Plus Asunaprevir in Patients Previously
Receiving Triple Therapy with Simeprevir
Yoshihito Uchida, Nobuaki Nakayama, Jun-ichi Kouyama, Kayoko
Naiki, Hayato Uemura, Kayoko Sugawara, Mie Inao, Satoshi
Mochida; Department of Gastroenterology and Hepatology,
Saitama Medical University, Iruma-gun, Saitama, Japan
Aim: Dual oral therapy with daclatasvir (DCV) plus asunaprevir
(ASV) was approved in Japan for patients with genotype 1b
HCV in July 2014. We established a novel system to quantify
NS5A-RAVs using cycling-probe real-time PCR (PLos One
2014), and performed the therapy by priority for these without
baseline RAVs. However, rare RAVs showing extreme resistance
to NS5A inhibitors developed frequently during DCV/
ASV administrations especially in those with preveious triple
therapy with simeprevir (SMV) despite that baseline RAVs were
absent. We report on this serious problem. Methods: A total
of 224 patients (98 men. 126 women; 23 to 87 years old.)
received DCV/ASV for 24 weeks. Among them, 5 patients had
a history of virologic failure after combined SMV/Peg-IFN/
ribavirin therapy. RAVs in NS3 and NS5A regions at baseline
and during the therapies were evaluated by cycling-probe realtime
PCR combined with direct sequencing. Results: Baseline
Y93H and L31M mutations were found in 27 (12%) and 6
(2%) patients, respectively, while those with both mutations
were absent. The therapy has already been completed in 156
patients, and SVR4-12 was achieved in 134 patients (86%);
117 (91%) of 129 without NS5A-RAVs, 11 (52%) of 21 with
Y93H mutation and all of 6 with L31M mutations. Baseline
NS5A-RAVs were absent in 5 patients with previous therapies
including SMV, but virologic failure developed in all of them;
DCV/ASV was discontinued at 4 weeks in 2 due to null-response,
at 8 weeks in 2 due to virologic rebound and at 20
weeks in 1 due to breakthrough. Among them, both Y93H and
L31M mutations were detected only in 1 patient showing virologic
rebound, while were absent in the remaining 4 patients.