Abstract
Background: In the Phase II SOLAR-1 study, 12 or 24 weeks of ledipasvir/sofosbuvir and ribavirin yielded high sustained virological response rates at 12 weeks (SVR12) in patients with chronic HCV infection and advanced liver disease, including untransplanted patients with decompensated cirrhosis and liver transplant recipients with all stages of liver disease. Methods: We performed a post hoc analysis using data from this study to investigate associations between baseline characteristics and early on-treatment HCV RNA, and to determine the utility of early virological response (week 2 and 4) to predict SVR12. Serum HCV RNA was quantified using the Roche COBAS® Ampliprep®/Cobas TaqMan HCV Test, Version 2.0 with a lower limit of quantification (LLOQ) of 15 IU/ml. Results: Most patients achieved HCV RNA <LLOQ by treatment week 4 and target not detected (TND) by week 6. Baseline factors significantly associated with HCV RNA <LLOQ at week 2 were low HCV RNA (<800,000 IU/ml), absence of cirrhosis, age <60 years and no prior treatment experience. At week 4, low HCV RNA, absence of cirrhosis and IL28B CC were associated with <LLOQ, TND. No baseline factors were associated with week 6 response. There was no association between early on-treatment HCV RNA and SVR12. Conclusions: On-treatment HCV RNA quantification is of limited clinical use in patients with advanced liver disease and/or liver transplantation and does not predict SVR12. ClinicalTrials.gov: NCT01938430.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 541-546 |
| Number of pages | 6 |
| Journal | Antiviral Therapy |
| Volume | 21 |
| Issue number | 6 |
| DOIs | |
| State | Published - 2016 |
Funding
TMW, RH, PSP, SZ, NA participated in the conception and design of the post hoc analysis. TMW and David McNeel (Gilead Sciences, Inc., Foster City, CA, USA) have written the manuscript. ML has conducted the data analyses. All other authors critically revised draft versions of the report and approved the inal version for publication. The sponsor (Gilead Sciences) collected the data, monitored the study conduct and performed the statistical analyses. Trial registration details: NCT01938430 (ClinicalTrials. gov database). TMW has served on advisory boards for AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim and Janssen; has served as a speaker for AbbVie, Bristol-Myers Squibb and Janssen. KRR has served on advisory boards for AbbVie, Bristol-Myers Squibb, Merck, Gilead, Janssen and has received research support (money paid to institution) from AbbVie, Bristol-Myers Squibb, Merck, Gilead and Janssen. SLF has served as consultant and/or received grants from AbbVie, Bristol-Myers Squibb, Gilead, Janssen and Merck. MC has received research support and grants from Gilead. GTE has received research support and grants from AbbVie, BMS, Eisai, Gilead, Janssen, Merck and Roche/Genentech; and has served on advisory boards for AbbVie, BMS, Gilead, Janssen and Merck. SZ has served as consultant for AbbVie, Bristol-Myers Squibb, Gilead, Janssen and Merck/MSD. NA has received research support and grants from AbbVie, BMS and Gilead; has served on advisory boards for Gilead; has served as a consultant for Gilead; and has received personal fees from AbbVie, Achillion, BMS, Merck, Janssen and SprinBank. RH, JD, ML, PSP and JGM are employees of Gilead.
ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)
- Infectious Diseases
