TY - JOUR
T1 - Treatment of acute hepatitis C genotypes 1 and 4 with 8 weeks of grazoprevir plus elbasvir (DAHHS2)
T2 - an open-label, multicentre, single-arm, phase 3b trial
AU - Boerekamps, Anne
AU - De Weggheleire, Anja
AU - van den Berk, Guido E.
AU - Lauw, Fanny N.
AU - Claassen, Mark A. A.
AU - Posthouwer, Dirk
AU - Bierman, Wouter F.
AU - Hullegie, Sebastiaan J.
AU - Popping, Stephanie
AU - van de Vijver, David A. C. M.
AU - Dofferhoff, Anthonius S. M.
AU - Kootstra, Gert Jan
AU - Leyten, Eliane M.
AU - den Hollander, Jan
AU - van Kasteren, Marjo E.
AU - Soetekouw, Robert
AU - Ammerlaan, Heidi S. M.
AU - Schinkel, Janke
AU - Florence, Eric
AU - Arends, Joop E.
AU - Rijnders, Bart J. A.
N1 - Funding Information:
The study was investigator-initiated (by BJAR) and was supported by a research grant to BJAR from Merck Sharp and Dohme and Health-Holland. Merck Sharp and Dohme provided the study drugs free of charge. We thank Andre Boonstra and Gertine van Oord for logistical support in the lab. We thank Lida van Petersen, Imke Hooijenga, Inge de Kroon, Danielle van Elst, Nienke Langebeek, Gerjanne ter Beest, Robin Ackens, Karin Grintjes, Lida Beneken Kolmer, Corine Delsing, Sieds Wildenbeest, Lia Meerkerk, Jannigje Smit, and Marien Kuipers for local study coordination. We thank Sjoerd Rebers and Jelle Koopsen for phylogenetic analysis. We thank all patients that made the study a success.
Funding Information:
WFB reports grants and non-financial support from Janssen, outside the submitted work. SJH reports grants from Merck during the conduct of the study, and non-financial support from Gilead Sciences and Merck Sharp and Dohme outside the submitted work. SP reports grants from Gilead Sciences, ViiV Healthcare, Janssen, and Merck Sharp and Dohme during the conduct of the study. DACMvdV reports grants and travel support from ViiV Healthcare, and grants from Merck Sharp and Dohme, Janssen, and Gilead Sciences outside the submitted work. JdH reports advisory board fees from AbbVie, Gilead Sciences, and ViiV Healthcare outside the submitted work. JS reports grants from Gilead Sciences, AbbVie, Merck Sharp and Dohme, and Janssen Pharmaceuticals outside the submitted work. EF reports grants from Janssen, Gilead Sciences, and ViiV Healthcare, and acted on advisory boards for Janssen and ViiV Healthcare, outside the submitted work. JEA reports acting on advisory boards, with renumeration being paid to their institution, for Gilead Sciences, Janssen, AbbVie, Merck Sharp and Dohme, ViiV Healthcare, and Bristol-Myers Squibb, and grants from ViiV Healthcare, Merck Sharp and Dohme, Bristol-Myers Squibb, and AbbVie, outside the submitted work. BJAR reports grants from Merck Sharp and Dohme, during the conduct of the study; and grants from Gilead Sciences, and participation in advisory boards and travel support from Merck Sharp and Dohme, Janssen-Cilag, Bristol-Myers Squibb, Gilead Sciences, Pfizer, and ViiV Healthcare, outside the submitted work. All other authors declare no competing interests.
Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/4
Y1 - 2019/4
N2 - 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. Copyright (C) 2019 Elsevier Ltd. All rights reserved.
AB - 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. Copyright (C) 2019 Elsevier Ltd. All rights reserved.
KW - HUMAN-IMMUNODEFICIENCY-VIRUS
KW - HIV-INFECTED MEN
KW - ACUTE HCV
KW - SEX
KW - SOFOSBUVIR
KW - RIBAVIRIN
KW - REINFECTION
KW - COINFECTION
KW - COMBINATION
KW - INTERFERON
U2 - 10.1016/S2468-1253(18)30414-X
DO - 10.1016/S2468-1253(18)30414-X
M3 - Article
SN - 2468-1253
VL - 4
SP - 269
EP - 277
JO - The Lancet Gastroenterology and Hepatology
JF - The Lancet Gastroenterology and Hepatology
IS - 4
ER -