A pilot study of safety and efficacy of HCV retreatment with sofosbuvir/velpatasvir/voxilaprevir in patients with or without HIV (RESOLVE STUDY)

J Hepatol. 2019 Sep;71(3):498-504. doi: 10.1016/j.jhep.2019.05.021. Epub 2019 Jun 5.


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.

Keywords: HIV; Hepatitis C; Retreatment after virologic failure, resistance-associated substitutions.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aminoisobutyric Acids
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Carbamates / adverse effects
  • Carbamates / therapeutic use*
  • Cyclopropanes
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Genotype
  • HIV Infections / complications*
  • HIV-1 / genetics*
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Heterocyclic Compounds, 4 or More Rings / adverse effects
  • Heterocyclic Compounds, 4 or More Rings / therapeutic use*
  • Humans
  • Lactams, Macrocyclic
  • Leucine / analogs & derivatives
  • Macrocyclic Compounds / adverse effects
  • Macrocyclic Compounds / therapeutic use*
  • Male
  • Middle Aged
  • Pilot Projects
  • Proline / analogs & derivatives
  • Quinoxalines
  • RNA, Viral / genetics
  • Recurrence
  • Sofosbuvir / adverse effects
  • Sofosbuvir / therapeutic use*
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use*
  • Sustained Virologic Response*


  • Aminoisobutyric Acids
  • Antiviral Agents
  • Carbamates
  • Cyclopropanes
  • Heterocyclic Compounds, 4 or More Rings
  • Lactams, Macrocyclic
  • Macrocyclic Compounds
  • Quinoxalines
  • RNA, Viral
  • Sulfonamides
  • voxilaprevir
  • Proline
  • Leucine
  • velpatasvir
  • Sofosbuvir