Anne Boerekamps1, Anja De Weggheleire2, Guido E van den Berk3, Fanny N Lauw4, Mark A A Claassen5, Dirk Posthouwer6, Wouter F Bierman7, Sebastiaan J Hullegie8, Stephanie Popping9, David A C M van de Vijver9, Anthonius S M Dofferhoff10, Gert Jan Kootstra11, Eliane M Leyten12, Jan den Hollander13, Marjo E van Kasteren14, Robert Soetekouw15, Heidi S M Ammerlaan16, Janke Schinkel17, Eric Florence2, Joop E Arends18, Bart J A Rijnders8. 1. Department of Internal Medicine and Infectious Diseases, Erasmus MC, Rotterdam, Netherlands. Electronic address: anneboerekamps@gmail.com. 2. Department of Clinical Sciences, Institute of Tropical Medicine Antwerp, Antwerp, Belgium. 3. Department of Internal Medicine and Infectious Diseases, OLVG, Amsterdam, Netherlands. 4. Department of Internal Medicine and Infectious Diseases, Slotervaart MC, Amsterdam, Netherlands. 5. Department of Internal Medicine and Infectious Diseases, Rijnstate Ziekenhuis, Arnhem, Netherlands. 6. Department of Internal Medicine and Medical Microbiology, Maastricht UMC+, Maastricht, Netherlands. 7. Department of Internal Medicine and Infectious Diseases, Universitair Medisch Centrum Groningen, Groningen, Netherlands. 8. Department of Internal Medicine and Infectious Diseases, Erasmus MC, Rotterdam, Netherlands. 9. Department of Viroscience, Erasmus MC, Rotterdam, Netherlands. 10. Department of Internal Medicine and Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands. 11. Department of Internal Medicine and Infectious Diseases, Medisch Spectrum Twente, Enschede, Netherlands. 12. Department of Internal Medicine and Infectious Diseases, MC Haaglanden, The Hague, Netherlands. 13. Department of Internal Medicine and Infectious Diseases, Maasstad Ziekenhuis, Rotterdam, Netherlands. 14. Department of Internal Medicine and Infectious Diseases, Elisabeth-TweeSteden Ziekenhuis, Tilburg, Netherlands. 15. Department of Internal Medicine and Infectious Diseases, Spaarne Gasthuis, Haarlem, Netherlands. 16. Department of Internal Medicine, Catharina Hospital, Eindhoven, Netherlands. 17. Department of Medical Microbiology, Section of Clinical Virology, Academic Medical Center, Amsterdam, Netherlands. 18. Department of Internal Medicine and Infectious Diseases, Universitair Medisch Centrum Utrecht, Utrecht University, Utrecht, Netherlands.
Abstract
BACKGROUND: Direct-acting antivirals effectively treat chronic hepatitis C virus (HCV) infection but there is a paucity of data on their efficacy for acute HCV, when immediate treatment could prevent onward transmission. We assessed the efficacy of grazoprevir plus elbasvir treatment in acute HCV infection and investigated whether treatment can be shortened during the acute phase of HCV infection. METHODS: The Dutch Acute HCV in HIV study number 2 (DAHHS2) study was a single-arm, open-label, multicentre, phase 3b trial. Adult patients (≥18 years) with acute HCV genotype 1 or 4 infection (duration of infection 26 weeks or less, according to presumed day of infection) were recruited at 15 HIV outpatient clinics in the Netherlands and Belgium. All patients were treated with 8 weeks of grazoprevir 100 mg plus elbasvir 50 mg administered as one oral fixed drug combination tablet once daily. The primary efficacy endpoint was sustained virological response at 12 weeks after the end of treatment (SVR12; HCV RNA <15 IU/mL) in all patients who started treatment. Reinfection with a different HCV virus was not considered treatment failure in the primary analysis. This trial is registered with ClinicalTrials.gov, number NCT02600325. FINDINGS: Between Feb 15, 2016, and March 2, 2018, we assessed 146 patients with a recently acquired HCV infection for eligibility, of whom 86 were enrolled and 80 initiated therapy, all within 6 months after infection. All patients who initiated treatment completed treatment and no patients were lost to follow-up. 79 (99%, 95% CI 93-100) of 80 patients achieved SVR12. All 14 patients who were infected with a virus carrying a clinically significant polymorphism in NS5A were cured. If reinfections were considered treatment failures, 75 (94%, 86-98) of 80 patients achieved SVR12. Two serious adverse events not considered related to the treatment were reported (traumatic rectal bleeding and low back surgery). The most common adverse event was a new sexually transmitted infection (19 [24%] of 80 patients). The most common reported possibly drug-related adverse events were fatigue (11 [14%] patients), headache (seven [9%] patients), insomnia (seven [9%] patients), mood changes (five [6%] patients), dyspepsia (five [6%] patients), concentration impairment (four [5%] patients), and dizziness (4 [5%] patients), all of which were regarded as mild by the treating physician. No adverse events led to study drug discontinuation. INTERPRETATION: 8 weeks of grazoprevir plus elbasvir was highly effective for the treatment of acute HCV genotype 1 or 4 infection. The ability to treat acute HCV immediately after diagnosis might help physicians to reach the WHO goal of HCV elimination by 2030. FUNDING: Merck Sharp and Dohme and Health-Holland.
BACKGROUND: Direct-acting antivirals effectively treat chronic hepatitis C virus (HCV) infection but there is a paucity of data on their efficacy for acute HCV, when immediate treatment could prevent onward transmission. We assessed the efficacy of grazoprevir plus elbasvir treatment in acute HCV infection and investigated whether treatment can be shortened during the acute phase of HCV infection. METHODS: The Dutch Acute HCV in HIV study number 2 (DAHHS2) study was a single-arm, open-label, multicentre, phase 3b trial. Adult patients (≥18 years) with acute HCV genotype 1 or 4 infection (duration of infection 26 weeks or less, according to presumed day of infection) were recruited at 15 HIV outpatient clinics in the Netherlands and Belgium. All patients were treated with 8 weeks of grazoprevir 100 mg plus elbasvir 50 mg administered as one oral fixed drug combination tablet once daily. The primary efficacy endpoint was sustained virological response at 12 weeks after the end of treatment (SVR12; HCV RNA <15 IU/mL) in all patients who started treatment. Reinfection with a different HCV virus was not considered treatment failure in the primary analysis. This trial is registered with ClinicalTrials.gov, number NCT02600325. FINDINGS: Between Feb 15, 2016, and March 2, 2018, we assessed 146 patients with a recently acquired HCV infection for eligibility, of whom 86 were enrolled and 80 initiated therapy, all within 6 months after infection. All patients who initiated treatment completed treatment and no patients were lost to follow-up. 79 (99%, 95% CI 93-100) of 80 patients achieved SVR12. All 14 patients who were infected with a virus carrying a clinically significant polymorphism in NS5A were cured. If reinfections were considered treatment failures, 75 (94%, 86-98) of 80 patients achieved SVR12. Two serious adverse events not considered related to the treatment were reported (traumatic rectal bleeding and low back surgery). The most common adverse event was a new sexually transmitted infection (19 [24%] of 80 patients). The most common reported possibly drug-related adverse events were fatigue (11 [14%] patients), headache (seven [9%] patients), insomnia (seven [9%] patients), mood changes (five [6%] patients), dyspepsia (five [6%] patients), concentration impairment (four [5%] patients), and dizziness (4 [5%] patients), all of which were regarded as mild by the treating physician. No adverse events led to study drug discontinuation. INTERPRETATION: 8 weeks of grazoprevir plus elbasvir was highly effective for the treatment of acute HCV genotype 1 or 4 infection. The ability to treat acute HCV immediately after diagnosis might help physicians to reach the WHO goal of HCV elimination by 2030. FUNDING: Merck Sharp and Dohme and Health-Holland.
Authors: Stephanie Popping; Rosanne Verwijs; Lize Cuypers; Mark A Claassen; Guido E van den Berk; Anja De Weggheleire; Joop E Arends; Anne Boerekamps; Richard Molenkamp; Marion P Koopmans; Annelies Verbon; Charles A B Boucher; Bart J Rijnders; David A M C van de Vijver Journal: Clin Infect Dis Date: 2020-11-05 Impact factor: 9.079
Authors: Stephanie Popping; Lize Cuypers; Mark A A Claassen; Guido E van den Berk; Anja De Weggheleire; Joop E Arends; Anne Boerekamps; Richard Molenkamp; Marion P G Koopmans; Annelies Verbon; Charles A B Boucher; Bart Rijnders; David A M C van de Vijver Journal: Viruses Date: 2022-09-02 Impact factor: 5.818
Authors: Stephanie Popping; Brooke Nichols; Bart Rijnders; Jeroen van Kampen; Annelies Verbon; Charles Boucher; David van de Vijver Journal: J Virus Erad Date: 2019-11-04