Author information

¹Hepatology Unit, Hôpital Haut Lévêque, Bordeaux University Hospital, Bordeaux, & INSERM U1312, Bordeaux University, Bordeaux, France.

²CHU Rennes, Inserm, CIC 1414, Rennes, France.

³Université Paris Cité; Centre Hospitalier Cochin Port Royal, DMU Cancérologie et spécialités médico-chirurgicales, Service d'Hépatologie, Paris, France.

⁴Infectious Diseases Department, Hôpital de la Croix Rousse, Lyon University Hospitals, Lyon, France.

⁵Sorbonne Université, Inserm IMPLESP, Infectious Diseases Unit, St Antoine Hospital, AP-HP, Paris, France.

⁶Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire, Grenoble, France.

⁷Assistance Publique des Hôpitaux de Paris, Hôpital Saint-Louis, Service des Maladies Infectieuses et Tropicales, Paris, France.

⁸Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire, Dijon, France.

⁹Service de Maladies Infectieuses, Centre Hospitalier Universitaire, Nantes, France.

¹⁰Service d'Hépato-Gastroentérologie, Centre Hospitalier Inter-communal, Créteil, France.

¹¹Assistance Publique des Hôpitaux de Paris, Hôpital Bichat Claude Bernard, Service des Maladies Infectieuses et Tropicales, Paris, France.

¹²Sorbonne Université, Institute of Cardiometabolism and Nutrition, Hospital Pitié Salpêtrière, Paris, France.

¹³Hepatologie, Hôpital Avicenne, AP-HP, Avicenne, France.

¹⁴Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire, Montpellier, France.

¹⁵Service d'Héatologie, AP-HP Henri Mondor, Créteil, France.

¹⁶Hepato-gastroenterology Department, University Hospital Center and INSERM U 1248, Limoges University, Limoges, France.

¹⁷Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire, Lille, France.

¹⁸France Assistance Publique des Hôpitaux de Paris, Hôpital Tenon, Service des Maladies Infectieuses et Tropicales, Paris, France.

¹⁹CHU Rennes, Service des Maladies du Foie, Rennes, France.

²⁰Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire, Toulouse, France.

²¹Hospices Civils de Lyon, Hôpital Edouard Herriot, Fédération des Spécialités digestives, et Université Claude Bernard Lyon 1, Lyon, France.

²²Service d'Hépato-Gastroentérologie, Centre Hospitalier Général, Avignon, France.

²³Université 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.

²⁴France Assistance Publique des Hôpitaux de Paris, Hôpital Paul Brousse, Service d'Hépatologie, Villejuif, France.

²⁵Service d'Hépato-Gastroentérologie, Centre Hospitalier Général, Saint-Brieuc, France.

²⁶Sorbonne University, Infectious Diseases Department, Pitié-Salpêtrière Hospital, AP-HP, Pierre Louis Epidemiology and Public Health Institute (iPLESP), INSERM U1136, Paris, France.

²⁷Service de Virologie, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France.

²⁸National Reference Centre for Viral Hepatitis B, C and Delta, Department of Virology, Paris-Seine-Saint-Denis University Hospitals, Bobigny, France.

²⁹ANRS MIE, PariSanté Campus, 2 rue d'Oradour sur Glane, Paris, France.

³⁰Hepatology Department, Hospices Civils de Lyon, INSERM U1052-CRCL; Université Claude Bernard Lyon 1, Lyon, France.

Abstract

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 + pegIFN? 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 + pegIFN? 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 pegIFN? 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.