PMID- 31173815
OWN - NLM
STAT- MEDLINE
DCOM- 20201207
LR  - 20240224
IS  - 1600-0641 (Electronic)
IS  - 0168-8278 (Print)
IS  - 0168-8278 (Linking)
VI  - 71
IP  - 3
DP  - 2019 Sep
TI  - A pilot study of safety and efficacy of HCV retreatment with 
      sofosbuvir/velpatasvir/voxilaprevir in patients with or without HIV (RESOLVE 
      STUDY).
PG  - 498-504
LID - S0168-8278(19)30307-1 [pii]
LID - 10.1016/j.jhep.2019.05.021 [doi]
AB  - BACKGROUND & AIMS: Cure rates in response to retreatment with 
      sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) are high, but this regimen has 
      not been studied in patients with a history of poor adherence or treatment 
      interruption, nor in patients with HIV/HCV coinfection. Herein, we aimed to 
      assess the safety and efficacy of this combination in patients with genotype 1 
      HCV infection who had relapsed following combination direct-acting antiviral 
      (DAA) therapy, regardless of HIV infection or previous treatment course. METHODS: 
      The RESOLVE study was a multicenter, open-label, phase IIb study investigating 
      the safety, tolerability and efficacy of SOF/VEL/VOX in 77 patients with 
      virologic rebound following combination DAA therapy. Efficacy was defined as HCV 
      RNA below the lower limit of detection 12 weeks after the end of treatment 
      (SVR12), while safety endpoints included the incidence of grade 3 and 4 adverse 
      events (AEs) following treatment, and the proportion of patients who stopped 
      treatment prematurely due to AEs. RESULTS: In an intent-to-treat analysis, 70/77 
      (90.9%, 95% CI 82.1-95.8%) patients achieved SVR12, including 14/17 (82.4%) HIV 
      coinfected participants and 18/22 (81.8%) of those with previous non-completion 
      of DAA therapy. In an analysis of all patients who completed 12 weeks of study 
      medication, 70/71 patients (99%) achieved SVR12. One patient experienced a grade 
      3 AE, and 4 experienced a grade 4 AE, all unrelated to study participation. 
      Reported AEs were similar in HIV-coinfected patients, and patients receiving 
      dolutegravir-based antiretroviral treatment experienced no clinically significant 
      increases in aminotransferases. CONCLUSION: Retreatment with 12 weeks of 
      SOF/VEL/VOX was safe and effective in patients with relapsed HCV following 
      initial combination DAA-based treatment. Treatment response was not affected by 
      HIV coinfection or previous treatment course. LAY SUMMARY: Twelve weeks of the 
      combination of direct-acting antivirals (SOF/VEL/VOX) was safe and effective in 
      patients with relapsed hepatitis C virus infection who had previously received 
      combination therapy with direct-acting antivirals. Treatment response was not 
      diminished by HIV coinfection, or non-completion of previous direct-acting 
      antiviral-based therapy.
CI  - Copyright (c) 2019 European Association for the Study of the Liver. All rights 
      reserved.
FAU - Wilson, Eleanor
AU  - Wilson E
AD  - Division of Clinical Care and Research, Institute of Human Virology, University 
      of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address: 
      eleanor.wilson@ihv.umaryland.edu.
FAU - Covert, Emily
AU  - Covert E
AD  - Division of Clinical Care and Research, Institute of Human Virology, University 
      of Maryland School of Medicine, Baltimore, MD 21201, USA; Critical Care Medicine 
      Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, 
      USA.
FAU - Hoffmann, Jennifer
AU  - Hoffmann J
AD  - Division of Clinical Care and Research, Institute of Human Virology, University 
      of Maryland School of Medicine, Baltimore, MD 21201, USA.
FAU - Comstock, Emily
AU  - Comstock E
AD  - Division of Clinical Care and Research, Institute of Human Virology, University 
      of Maryland School of Medicine, Baltimore, MD 21201, USA.
FAU - Emmanuel, Benjamin
AU  - Emmanuel B
AD  - Division of Clinical Care and Research, Institute of Human Virology, University 
      of Maryland School of Medicine, Baltimore, MD 21201, USA.
FAU - Tang, Lydia
AU  - Tang L
AD  - Division of Clinical Care and Research, Institute of Human Virology, University 
      of Maryland School of Medicine, Baltimore, MD 21201, USA.
FAU - Husson, Jennifer
AU  - Husson J
AD  - Division of Clinical Care and Research, Institute of Human Virology, University 
      of Maryland School of Medicine, Baltimore, MD 21201, USA.
FAU - Chua, Joel
AU  - Chua J
AD  - Division of Clinical Care and Research, Institute of Human Virology, University 
      of Maryland School of Medicine, Baltimore, MD 21201, USA.
FAU - Price, Angie
AU  - Price A
AD  - Division of Clinical Care and Research, Institute of Human Virology, University 
      of Maryland School of Medicine, Baltimore, MD 21201, USA.
FAU - Mathur, Poonam
AU  - Mathur P
AD  - Division of Clinical Care and Research, Institute of Human Virology, University 
      of Maryland School of Medicine, Baltimore, MD 21201, USA.
FAU - Rosenthal, Elana
AU  - Rosenthal E
AD  - Division of Clinical Care and Research, Institute of Human Virology, University 
      of Maryland School of Medicine, Baltimore, MD 21201, USA.
FAU - Kattakuzhy, Sarah
AU  - Kattakuzhy S
AD  - Division of Clinical Care and Research, Institute of Human Virology, University 
      of Maryland School of Medicine, Baltimore, MD 21201, USA.
FAU - Masur, Henry
AU  - Masur H
AD  - Critical Care Medicine Department, Clinical Center, National Institutes of 
      Health, Bethesda, MD 20892, USA.
FAU - Kottilil, Shyam
AU  - Kottilil S
AD  - Division of Clinical Care and Research, Institute of Human Virology, University 
      of Maryland School of Medicine, Baltimore, MD 21201, USA.
LA  - eng
GR  - ZIA CL009018/ImNIH/Intramural NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190605
PL  - Netherlands
TA  - J Hepatol
JT  - Journal of hepatology
JID - 8503886
RN  - 0 (Aminoisobutyric Acids)
RN  - 0 (Antiviral Agents)
RN  - 0 (Carbamates)
RN  - 0 (Cyclopropanes)
RN  - 0 (Heterocyclic Compounds, 4 or More Rings)
RN  - 0 (Lactams, Macrocyclic)
RN  - 0 (Macrocyclic Compounds)
RN  - 0 (Quinoxalines)
RN  - 0 (RNA, Viral)
RN  - 0 (Sulfonamides)
RN  - 0570F37359 (voxilaprevir)
RN  - 9DLQ4CIU6V (Proline)
RN  - GMW67QNF9C (Leucine)
RN  - KCU0C7RS7Z (velpatasvir)
RN  - WJ6CA3ZU8B (Sofosbuvir)
SB  - IM
MH  - Aged
MH  - Aminoisobutyric Acids
MH  - Antiviral Agents/adverse effects/*therapeutic use
MH  - Carbamates/adverse effects/*therapeutic use
MH  - Cyclopropanes
MH  - Drug Therapy, Combination
MH  - Female
MH  - Follow-Up Studies
MH  - Genotype
MH  - HIV Infections/*complications
MH  - HIV-1/*genetics
MH  - Hepacivirus/*drug effects/genetics
MH  - Hepatitis C, Chronic/*complications/*drug therapy/virology
MH  - Heterocyclic Compounds, 4 or More Rings/adverse effects/*therapeutic use
MH  - Humans
MH  - Lactams, Macrocyclic
MH  - Leucine/analogs & derivatives
MH  - Macrocyclic Compounds/adverse effects/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Pilot Projects
MH  - Proline/analogs & derivatives
MH  - Quinoxalines
MH  - RNA, Viral/genetics
MH  - Recurrence
MH  - Sofosbuvir/adverse effects/*therapeutic use
MH  - Sulfonamides/adverse effects/*therapeutic use
MH  - *Sustained Virologic Response
PMC - PMC10885189
MID - NIHMS1959940
OTO - NOTNLM
OT  - HIV
OT  - Hepatitis C
OT  - Retreatment after virologic failure, resistance-associated substitutions
COIS- Dr. Wilson and Dr. Kottilil report an investigator-initiated grant and drug 
      support during the conduct of the study. Dr. Husson reports grants and 
      non-financial support from Merck, Sharpe, and Dome, outside the submitted work. 
      Dr. Tang, Ms. Price and Dr. Kattakuzhy report grants from Gilead Sciences, Inc. 
      outside the submitted work. Dr. Chua reports grants and personal fees from Gilead 
      Sciences Inc., outside the submitted work. Dr. Rosenthal reports grants and 
      non-financial support from Gilead Sciences, during the conduct of the study; 
      grants and non-financial support from Gilead Sciences, and grants and 
      non-financial support from Merck outside the submitted work. Dr. Kottilil reports 
      grants and other from Gilead Sciences, grants and other from Merck, and grants 
      from Arbutus during the conduct of the study. Ms. Covert, Ms. Hoffmann, Dr. 
      Emmanuel, Ms. Comstock, Dr. Mathur, and Dr. Masur have nothing to disclose. 
      Please refer to the accompanying ICMJE disclosure forms for further details.
EDAT- 2019/06/08 06:00
MHDA- 2020/12/15 06:00
PMCR- 2024/02/23
CRDT- 2019/06/08 06:00
PHST- 2019/02/28 00:00 [received]
PHST- 2019/04/30 00:00 [revised]
PHST- 2019/05/23 00:00 [accepted]
PHST- 2019/06/08 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2019/06/08 06:00 [entrez]
PHST- 2024/02/23 00:00 [pmc-release]
AID - S0168-8278(19)30307-1 [pii]
AID - 10.1016/j.jhep.2019.05.021 [doi]
PST - ppublish
SO  - J Hepatol. 2019 Sep;71(3):498-504. doi: 10.1016/j.jhep.2019.05.021. Epub 2019 Jun 
      5.