Patrick Miailhes1, Marianne Maynard-Muet2, Fanny Lebossé2, Fabrice Carrat3, Cécile Bouix2, Caroline Lascoux-Combe4, Philippe Sogni5, David Rey6, Yoann Barthe3, Stanislas Pol5, Patrice Cacoub7, Fabien Zoulim2, Lionel Piroth8. 1. Service des Maladies Infectieuses et Tropicales, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, INSERM U1052, Lyon, France. Electronic address: patrick.miailhes@chu-lyon.fr. 2. Service d'Hépatologie, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, INSERM U1052, Lyon, France. 3. UMRS-707, Université Paris 6 et INSERM, Santé Publique, APHP, Paris, France. 4. Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Louis, APHP, Paris, France. 5. Université Paris Descartes, Inserm U1016, Unité d'Hépatologie, APHP, Hôpital Cochin, Paris, France. 6. Center for HIV infection Care, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. 7. Hôpital de La Pitié-Salpêtrière, Service de Médecine Interne, CNRS UMR 7087, Univ Pierre et Marie Curie, Paris, France. 8. Service des Maladies Infectieuses, Hôpital du bocage, Université de Bourgogne, Dijon, France.
Abstract
BACKGROUND & AIMS: In hepatitis B e antigen (HBeAg) positive-HIV co-infected patients treated with combined antiretroviral therapy (cART), including tenofovir disoproxil fumarate (TDF), the rate of HBe seroconversion remains low. Whether adding pegylated interferon alfa (PegIFN) could increase the likelihood of HBeAg loss and HBe seroconversion has not been assessed. METHODS: A 48-week PegIFN therapy was added to HBeAg positive-HIV co-infected patients on TDF and emtricitabine, or lamivudine for at least 6 months. The primary endpoint was HBV sustained response: HBe seroconversion with undetectable HBV DNA levels 24 weeks after completing PegIFN therapy (W72). RESULTS: Fifty-one patients (49 men, median age 46 years, range: 32-65), were included. Median duration of HIV, HBV infections and TDF therapy was 10.3 (0.6-22), 9.8 (0.5-16), and 3.3 (0.5-6.8)years, respectively. Median baseline CD4 count was 506 (175-1316)/mm(3). HIV viral load was <50 copies/ml in 49 (96%) patients. Nine (18%) patients stopped PegIFN prematurely. Ten (20%) patients experienced HBeAg loss at W72 and four (8%) patients had a HBV sustained response. No HBs seroconversion was observed. Only patients with more than 350 CD4/mm(3) at baseline achieved HBe loss. HBeAg level >10 PEIU/ml at W12 or a quantitative HBsAg decline <0.5 log IU/ml at W24 had 100% and 84% negative predictive values for response, respectively. CONCLUSIONS: 48-week PegIFN additional therapy to cART including TDF did not significantly increase the HBe seroconversion rate, despite an HBeAg loss in 20% of the patients. HBe and HBs kinetics may nevertheless be of help in tailoring and optimising this strategy.
BACKGROUND & AIMS: In hepatitis B e antigen (HBeAg) positive-HIV co-infectedpatients treated with combined antiretroviral therapy (cART), including tenofovir disoproxil fumarate (TDF), the rate of HBe seroconversion remains low. Whether adding pegylated interferon alfa (PegIFN) could increase the likelihood of HBeAg loss and HBe seroconversion has not been assessed. METHODS: A 48-week PegIFN therapy was added to HBeAg positive-HIV co-infectedpatients on TDF and emtricitabine, or lamivudine for at least 6 months. The primary endpoint was HBV sustained response: HBe seroconversion with undetectable HBV DNA levels 24 weeks after completing PegIFN therapy (W72). RESULTS: Fifty-one patients (49 men, median age 46 years, range: 32-65), were included. Median duration of HIV, HBV infections and TDF therapy was 10.3 (0.6-22), 9.8 (0.5-16), and 3.3 (0.5-6.8)years, respectively. Median baseline CD4 count was 506 (175-1316)/mm(3). HIV viral load was <50 copies/ml in 49 (96%) patients. Nine (18%) patients stopped PegIFN prematurely. Ten (20%) patients experienced HBeAg loss at W72 and four (8%) patients had a HBV sustained response. No HBs seroconversion was observed. Only patients with more than 350 CD4/mm(3) at baseline achieved HBe loss. HBeAg level >10 PEIU/ml at W12 or a quantitative HBsAg decline <0.5 log IU/ml at W24 had 100% and 84% negative predictive values for response, respectively. CONCLUSIONS: 48-week PegIFN additional therapy to cART including TDF did not significantly increase the HBe seroconversion rate, despite an HBeAg loss in 20% of the patients. HBe and HBs kinetics may nevertheless be of help in tailoring and optimising this strategy.
Authors: Kasha P Singh; Megan Crane; Jennifer Audsley; Anchalee Avihingsanon; Joe Sasadeusz; Sharon R Lewin Journal: AIDS Date: 2017-09-24 Impact factor: 4.177
Authors: Stefan H E Kaufmann; Anca Dorhoi; Richard S Hotchkiss; Ralf Bartenschlager Journal: Nat Rev Drug Discov Date: 2017-09-22 Impact factor: 84.694