Treatment with bulevirtide in HIV-infected patients with chronic hepatitis D: ANRS HD EP01 BuleDelta and compassionate cohort
Victor de Lédinghen,
Claire Fougerou-Leurent,
Estelle Le Pabic,
Stanislas Pol,
Dulce Alfaiate,
Karine Lacombe,
Marie-Noëlle Hilleret,
Caroline Lascoux-Combe,
Anne Minello,
Eric Billaud,
Isabelle Rosa,
Anne Gervais,
Vlad Ratziu,
Nathalie Ganne,
Georges-Philippe Pageaux,
Vincent Leroy,
Véronique Loustaud-Ratti,
Philippe Mathurin,
Julie Chas,
Caroline Jezequel,
Sophie Métivier,
Jérôme Dumortier,
Jean-Pierre Arpurt,
Tarik Asselah,
Bruno Roche,
Antonia Le Gruyer,
Marc-Antoine Valantin,
Caroline Scholtès,
Emmanuel Gordien,
Christelle Tual,
Amel Kortebi,
Fatoumata Coulibaly,
Eric Rosenthal,
Miroslava Subic-Levrero,
Dominique Roulot,
Fabien Zoulim,
François Raffi,
Laurent Alric,
Patrick Miailhes,
Albert Tran,
Christiane Stern,
Xavier Causse,
Simona Tripon,
Ghassan Riachi,
Olivier Chazouillères,
Armando Abergel,
Louis d’Alteroche,
Jérôme Gournay,
Garance Lagadic,
Patrizia Carrieri,
Ségolène Brichler,
Martin Siguier,
Jessica Krause,
Juliette Foucher,
Souad Ben Ali,
Magdalena Meszaros,
Anne Varaut,
Valérie Canva
Affiliations
Victor de Lédinghen
Hepatology Unit, Hôpital Haut Lévêque, Bordeaux University Hospital, Bordeaux, & INSERM U1312, Bordeaux University, Bordeaux, France; Corresponding author. Address: Service d’Hepatologie, Hôpital Haut-Lévêque, 33604 Pessac Cedex, France. Tel.: +33-557-656-439; Fax: +33-557-656-445.
Claire Fougerou-Leurent
CHU Rennes, Inserm, CIC 1414, Rennes, France
Estelle Le Pabic
CHU Rennes, Inserm, CIC 1414, Rennes, France
Stanislas Pol
Université Paris Cité; Centre Hospitalier Cochin Port Royal, DMU Cancérologie et spécialités médico-chirurgicales, Service d’Hépatologie, Paris, France
Dulce Alfaiate
Infectious Diseases Department, Hôpital de la Croix Rousse, Lyon University Hospitals, Lyon, France
Karine Lacombe
Sorbonne Université, Inserm IMPLESP, Infectious Diseases Unit, St Antoine Hospital, AP-HP, Paris, France
Marie-Noëlle Hilleret
Service d’Hépato-Gastroentérologie, Centre Hospitalier Universitaire, Grenoble, France
Caroline Lascoux-Combe
Assistance Publique des Hôpitaux de Paris, Hôpital Saint-Louis, Service des Maladies Infectieuses et Tropicales, Paris, France
Anne Minello
Service d’Hépato-Gastroentérologie, Centre Hospitalier Universitaire, Dijon, France
Eric Billaud
Service de Maladies Infectieuses, Centre Hospitalier Universitaire, Nantes, France
Isabelle Rosa
Service d’Hépato-Gastroentérologie, Centre Hospitalier Inter-communal, Créteil, France
Anne Gervais
Assistance Publique des Hôpitaux de Paris, Hôpital Bichat Claude Bernard, Service des Maladies Infectieuses et Tropicales, Paris, France
Vlad Ratziu
Sorbonne Université, Institute of Cardiometabolism and Nutrition, Hospital Pitié Salpêtrière, Paris, France
Nathalie Ganne
Hepatologie, Hôpital Avicenne, AP-HP, Avicenne, France
Georges-Philippe Pageaux
Service d’Hépato-Gastroentérologie, Centre Hospitalier Universitaire, Montpellier, France
Vincent Leroy
Service d’Héatologie, AP-HP Henri Mondor, Créteil, France
Véronique Loustaud-Ratti
Hepato-gastroenterology Department, University Hospital Center and INSERM U 1248, Limoges University, Limoges, France
Philippe Mathurin
Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire, Lille, France
Julie Chas
France Assistance Publique des Hôpitaux de Paris, Hôpital Tenon, Service des Maladies Infectieuses et Tropicales, Paris, France
Caroline Jezequel
CHU Rennes, Service des Maladies du Foie, Rennes, France
Sophie Métivier
Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire, Toulouse, France
Jérôme Dumortier
Hospices Civils de Lyon, Hôpital Edouard Herriot, Fédération des Spécialités digestives, et Université Claude Bernard Lyon 1, Lyon, France
Jean-Pierre Arpurt
Service d'Hépato-Gastroentérologie, Centre Hospitalier Général, Avignon, France
Tarik Asselah
Université Paris-Cité, Centre de recherche sur l'inflammation, Inserm U1149, Department of Hepatology, Assistance Publique des Hôpitaux de Paris (AP-HP), Hôpital Beaujon, Clichy, France
Bruno Roche
France Assistance Publique des Hôpitaux de Paris, Hôpital Paul Brousse, Service d’Hépatologie, Villejuif, France
Antonia Le Gruyer
Service d'Hépato-Gastroentérologie, Centre Hospitalier Général, Saint-Brieuc, France
Marc-Antoine Valantin
Sorbonne University, Infectious Diseases Department, Pitié-Salpêtrière Hospital, AP-HP, Pierre Louis Epidemiology and Public Health Institute (iPLESP), INSERM U1136, Paris, France
Caroline Scholtès
Service de Virologie, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France
Emmanuel Gordien
National Reference Centre for Viral Hepatitis B, C and Delta, Department of Virology, Paris-Seine-Saint-Denis University Hospitals, Bobigny, France
Christelle Tual
CHU Rennes, Inserm, CIC 1414, Rennes, France
Amel Kortebi
CHU Rennes, Inserm, CIC 1414, Rennes, France
Fatoumata Coulibaly
ANRS MIE, PariSanté Campus, 2 rue d’Oradour sur Glane, Paris, France
Eric Rosenthal
ANRS MIE, PariSanté Campus, 2 rue d’Oradour sur Glane, Paris, France
Miroslava Subic-Levrero
Hepatology Department, Hospices Civils de Lyon, INSERM U1052-CRCL; Université Claude Bernard Lyon 1, Lyon, France
Dominique Roulot
Hepatologie, Hôpital Avicenne, AP-HP, Avicenne, France
Fabien Zoulim
Hepatology Department, Hospices Civils de Lyon, INSERM U1052-CRCL; Université Claude Bernard Lyon 1, Lyon, France
Background & Aims: In France, bulevirtide (BLV) became available in September 2019 through an early access program to treat patients with HDV. The aim of this analysis was to evaluate the efficacy and safety of BLV in patients with HIV and HDV coinfection. Methods: Patients received BLV 2 mg ± pegylated interferon-α (pegIFNα) according to the physician’s decision. The primary endpoint (per-protocol analysis) was the virological response rate at Week 48, defined as the proportion of patients with undetectable serum HDV RNA or a HDV RNA decline >2 log10 IU/ml from baseline. Results: The characteristics of the 38 patients were as follows: 28 male, mean age 47.7 years, and mean baseline HDV RNA viral load 5.7 ± 1.2 log10 IU/ml. Median HIV viral load and mean CD4 count were 32 (30–65) copies/ml and 566 ± 307/mm3, respectively. Eight patients stopped treatment before Week 48. At Week 48, 10 of 19 patients (52.6%) in the 2 mg BLV group and five of seven patients (71.4%) in the 2 mg BLV + pegIFNɑ group had reached virological response (no HDV RNA available in four patients). At Week 48, seven of 19 patients in the 2 mg BLV group and three of six patients in the 2 mg BLV + pegIFNɑ group had a combined response (virological response and normal alanine aminotransferase level). Conclusions: Adults living with HIV coinfected with HDV can be treated by BLV with a virological response in more than 50% of patients. The combination of BLV and pegIFNɑ showed a strong virological response. Impact and implications: Bulevirtide is the only EMA-approved drug for HDV treatment, and we showed that it can be used in adults living with HIV, with an overall good tolerability. Bulevirtide induces a virological response in more than 50% of patients, suggesting that bulevirtide should be considered as a first-line therapy in this specific population. Bulevirtide in combination with pegIFNα could be used in patients without pegIFNα contraindication. No specific drug–drug interaction is reported. Bulevirtide is the only EMA-approved drug for HDV treatment, and we showed that it can be used in adults living with HIV, with an overall good tolerability. Bulevirtide induces a virological response in more than 50% of patients, suggesting that bulevirtide should be considered as a first-line therapy in this specific population. Bulevirtide in combination with pegIFNα could be used in patients without pegIFNα contraindication. No specific drug–drug interaction is reported. Bulevirtide is the only EMA-approved drug for HDV treatment, and we showed that it can be used in adults living with HIV, with an overall good tolerability. Bulevirtide induces a virological response in more than 50% of patients, suggesting that bulevirtide should be considered as a first-line therapy in this specific population. Bulevirtide in combination with pegIFNα could be used in patients without pegIFNα contraindication. No specific drug–drug interaction is reported.