Anders Boyd1, Patrick Miailhes2, Julie Chas3, Marc-Antoine Valantin4, Yazdan Yazdanpanah5, Eric Rosenthal6, Stephane Chevaliez7, Lionel Piroth8, Hayette Rougier9, Gilles Peytavin10, Gilles Pialoux3,11, Pierre-Marie Girard12,13, Karine Lacombe12,13. 1. INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75012 Paris, France. 2. Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Service de Maladies Infectieuses et Tropicales, Lyon, France. 3. AP-HP, Hôpital Tenon, Service de Maladies Infectieuses et tropicales, Paris, France. 4. AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Maladies Infectieuses et tropicales, Paris, France. 5. AP-HP, Hôpital Bichat-Claude Bernard, Service de Maladies Infectieuses et tropicales, Paris, France. 6. Hôpital de l'Archet, Service de médecine interne, Nice, France. 7. AP-HP, département de Virologie, Hôpital Henri Mondor, National Reference Center for Viral Hepatitis B, C and delta, INSERM U955, Créteil, France. 8. Département d'infectiologie, CHU de Dijon, 21079 Dijon, France; INSERM CIC 1432, Université de Bourgogne, 21079 Dijon, France. 9. Institut de Médecine et d'Epidémiologie Appliquée, Paris. 10. AP-HP, Hôpital Bichat-Claude Bernard, Laboratoire de Pharmacologie-Toxicologie and IAME, UMR 1137, Université Paris Diderot, Sorbonne Paris Cité and INSERM, Paris, France. 11. Sorbonne Université, Paris, France. 12. Service de maladies infectieuses et tropicales, Hôpital St Antoine, AP-HP, Paris, France. 13. Sorbonne Université, INSERM UMR-S1136, Institut Pierre Louis de Santé Publique, Paris, France.
Abstract
BACKGROUND: In Europe, increases in HCV infection have been observed over the last two decades in MSM, making them a key population for recently acquired HCV. Alternative combinations of direct-acting antiviral agents against early HCV infection need to be assessed. PATIENTS AND METHODS: In this pilot trial, MSM with recently acquired genotype 1 or 4 HCV infection were prospectively included and received 8 weeks of oral grazoprevir 100 mg and elbasvir 50 mg in a fixed-dose combination administered once daily. The primary endpoint was sustained virological response evaluated 12 weeks after the end of treatment (EOT) (SVR12). Secondary endpoints were the virological characterization of failures, the quality of life before, during and after treatment and the rate of reinfection. RESULTS: In a 15 month period, 30 patients were enrolled, all of whom were MSM. Of the 29 patients completing follow-up, 28 (96%, 95% CI = 82%-99%) achieved SVR12. One patient interrupted follow-up (suicide) but had undetectable plasma HCV RNA at EOT. One patient with suboptimal adherence confirmed by plasma drug monitoring relapsed and developed NS3, NS5A and NS5B resistance-associated substitutions (V36M, M28V and S556G). The most common adverse events related to study drug were diarrhoea (n = 4, 13%), insomnia (n = 2, 7%) and fatigue (n = 2, 7%), although no patient discontinued treatment. No HIV RNA breakthrough was reported in the 28 patients with HIV coinfection. At Week 48, reinfection was diagnosed in three patients. CONCLUSIONS: Our data support the use of grazoprevir/elbasvir for immediate treatment against HCV in order to reduce HCV transmission in MSM.
BACKGROUND: In Europe, increases in HCV infection have been observed over the last two decades in MSM, making them a key population for recently acquired HCV. Alternative combinations of direct-acting antiviral agents against early HCV infection need to be assessed. PATIENTS AND METHODS: In this pilot trial, MSM with recently acquired genotype 1 or 4 HCV infection were prospectively included and received 8 weeks of oral grazoprevir 100 mg and elbasvir 50 mg in a fixed-dose combination administered once daily. The primary endpoint was sustained virological response evaluated 12 weeks after the end of treatment (EOT) (SVR12). Secondary endpoints were the virological characterization of failures, the quality of life before, during and after treatment and the rate of reinfection. RESULTS: In a 15 month period, 30 patients were enrolled, all of whom were MSM. Of the 29 patients completing follow-up, 28 (96%, 95% CI = 82%-99%) achieved SVR12. One patient interrupted follow-up (suicide) but had undetectable plasma HCV RNA at EOT. One patient with suboptimal adherence confirmed by plasma drug monitoring relapsed and developed NS3, NS5A and NS5B resistance-associated substitutions (V36M, M28V and S556G). The most common adverse events related to study drug were diarrhoea (n = 4, 13%), insomnia (n = 2, 7%) and fatigue (n = 2, 7%), although no patient discontinued treatment. No HIV RNA breakthrough was reported in the 28 patients with HIV coinfection. At Week 48, reinfection was diagnosed in three patients. CONCLUSIONS: Our data support the use of grazoprevir/elbasvir for immediate treatment against HCV in order to reduce HCV transmission in MSM.