David Rey1, Lionel Piroth2, Marie-Josée Wendling3, Patrick Miailhes4, Marie-Louise Michel5, Cécilie Dufour6, Georges Haour6, Philippe Sogni7, Alexandra Rohel8, Faiza Ajana9, Eric Billaud10, Jean-Michel Molina11, Odile Launay12, Fabrice Carrat13. 1. Le Trait d'Union, Center for HIV Care, Hôpitaux Universitaires Strasbourg, France. Electronic address: david.rey@chru-strasbourg.fr. 2. Département d'Infectiologie, CHU Dijon, and UMR 1347, Université de Bourgogne, Dijon, France. 3. Laboratoire de Virologie, Hôpitaux Universitaires Strasbourg, France. 4. Service des Maladies Infectieuses et Tropicales, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France. 5. Laboratoire de Pathogenèse des virus de l'hépatite B, Institut Pasteur, Paris. 6. Institut National de la Santé et de la Recherche Médicale, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France. 7. Service d'hépatologie, Hôpital Cochin, Paris, France. 8. Agence Nationale De Recherche Sur Le Sida Et Les Hépatites (ANRS), Paris, France. 9. Service des Maladies Infectieuses et Tropicales, Hôpital Gustave Dron, Tourcoing, France. 10. Service des Maladies Infectieuses et Tropicales, CHU Nantes, Nantes, France. 11. Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Louis, Paris, France. 12. Université Paris Descartes, Sorbonne Paris Cité, and Inserm CIC 1417, and Assistance Publique Hôpitaux de Paris, Hôpital Cochin, CIC Cochin Pasteur, Paris, France. 13. Institut National de la Santé et de la Recherche Médicale, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France; Sorbonne Universités, UPMC Université Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France; Département de santé publique, Groupe Hospitalier Est Parisien, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France.
Abstract
BACKGROUND:Revaccination with double-dose hepatitis B vaccine has been recommended in HIV-infected patients who do not respond to standard vaccination, but has not yet been assessed. We aimed to compare the safety and immunogenicity of a reinforced hepatitis B revaccination protocol with the standard revaccination schedule in HIV-infected patients not responding to primary vaccination. METHODS: We did this multicentre, open-label, randomised controlled trial, at 53 centres in France. HIV-infected adults (aged ≥18 years), with CD4 counts of 200 cells per μL or more and no response to a previous hepatitis B vaccination or a 20 μg booster dose, were randomly assigned (1:1), according to a computer-generated randomisation list with permuted blocks (block sizes of two to six), to receive either standard-dose (20 μg) or double-dose (40 μg) recombinant hepatitis B vaccine at weeks 0, 4, and 24. Randomisation was stratified by baseline CD4 count (200-349 vs ≥350 cells per μL). Patients and treating physicians were not masked to treatment allocation, but the randomisation list was concealed from the investigators who assigned participants to the vaccination groups. The primary endpoint was the proportion of responders, defined as patients with hepatitis B surface antibody (anti-HBs) titres of 10 mIU/mL or more, at week 28. We did analysis by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT00670839. FINDINGS:Between May 19, 2008, and May 8, 2011, 178 participants were randomly assigned to the standard-dose group (n=90) or the double-dose group (n=88), of whom 176 (98%) participants were included in the primary efficacy analysis. At week 28, we recorded a response in 60 patients (67%, 95% CI 57-77) in the standard-dose group versus 64 patients (74%, 63-82) in the double-dose group (p=0·334). Except for more frequent local reactions in the double-dose group than the standard-dose group (13 [15%] vs four [4%] patients; p=0·020), there was no difference in safety between groups. INTERPRETATION: In adults with HIV-1 who have not responded to previous hepatitis B vaccination, double-dose revaccination did not achieve a higher response rate than did revaccination with standard single-dose regimen. However, the safety profile was similar between treatment groups. Our results should be assessed in future studies before double-dose vaccine can be considered for the standard of care of vaccine non-responders. FUNDING: French National Institute for Medical Research-French National Agency for Research on AIDS and Viral Hepatitis.
RCT Entities:
BACKGROUND: Revaccination with double-dose hepatitis B vaccine has been recommended in HIV-infectedpatients who do not respond to standard vaccination, but has not yet been assessed. We aimed to compare the safety and immunogenicity of a reinforced hepatitis B revaccination protocol with the standard revaccination schedule in HIV-infectedpatients not responding to primary vaccination. METHODS: We did this multicentre, open-label, randomised controlled trial, at 53 centres in France. HIV-infected adults (aged ≥18 years), with CD4 counts of 200 cells per μL or more and no response to a previous hepatitis B vaccination or a 20 μg booster dose, were randomly assigned (1:1), according to a computer-generated randomisation list with permuted blocks (block sizes of two to six), to receive either standard-dose (20 μg) or double-dose (40 μg) recombinant hepatitis B vaccine at weeks 0, 4, and 24. Randomisation was stratified by baseline CD4 count (200-349 vs ≥350 cells per μL). Patients and treating physicians were not masked to treatment allocation, but the randomisation list was concealed from the investigators who assigned participants to the vaccination groups. The primary endpoint was the proportion of responders, defined as patients with hepatitis B surface antibody (anti-HBs) titres of 10 mIU/mL or more, at week 28. We did analysis by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT00670839. FINDINGS: Between May 19, 2008, and May 8, 2011, 178 participants were randomly assigned to the standard-dose group (n=90) or the double-dose group (n=88), of whom 176 (98%) participants were included in the primary efficacy analysis. At week 28, we recorded a response in 60 patients (67%, 95% CI 57-77) in the standard-dose group versus 64 patients (74%, 63-82) in the double-dose group (p=0·334). Except for more frequent local reactions in the double-dose group than the standard-dose group (13 [15%] vs four [4%] patients; p=0·020), there was no difference in safety between groups. INTERPRETATION: In adults with HIV-1 who have not responded to previous hepatitis B vaccination, double-dose revaccination did not achieve a higher response rate than did revaccination with standard single-dose regimen. However, the safety profile was similar between treatment groups. Our results should be assessed in future studies before double-dose vaccine can be considered for the standard of care of vaccine non-responders. FUNDING: French National Institute for Medical Research-French National Agency for Research on AIDS and Viral Hepatitis.
Authors: Norah A Terrault; Anna S F Lok; Brian J McMahon; Kyong-Mi Chang; Jessica P Hwang; Maureen M Jonas; Robert S Brown; Natalie H Bzowej; John B Wong Journal: Hepatology Date: 2018-04 Impact factor: 17.425
Authors: Robert M Paris; Lucimar G Milagres; Eirini Moysi; Jason F Okulicz; Brian K Agan; Anu Ganesan; Constantinos Petrovas; Richard A Koup Journal: Pathog Immun Date: 2017-03-14