Odile Launay1, Arielle R Rosenberg2, David Rey3, Noelle Pouget4, Marie-Louise Michel5, Jacques Reynes6, Didier Neau7, Francois Raffi8, Lionel Piroth9, Fabrice Carrat10. 1. Université Paris Descartes, Sorbonne Paris Cité, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Cochin, Paris, France2Institut National de la Santé et de la Recherche Medicale (INSERM), Clinical Investigation Center 1417, Paris, France3INSERM Fren. 2. Université Paris Descartes, Sorbonne Paris Cité, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Cochin, Paris, France. 3. Hôpitaux Universitaires, Strasbourg, France. 4. Sorbonne Universités, Université Pierre-et-Marie-Curie, Université Paris 06, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique (Unité Mixte de Recherche en Santé 1136), Paris, France. 5. Institut Pasteur, INSERM U994, Paris, France. 6. INSERM French Clinical Research Infrastructure Network, Innovative Clinical Research Network in Vaccinology, France7Centre Hospitalier Universitaire de Montpellier, Hôpital Gui de Chauliac, Université de Montpellier, Unité Mixte Internationale 233, Montpe. 7. Service des Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire (CHU) Bordeaux, Unité Mixte de Recherche-Centre National de la Recherche Scientifique 5234, Bordeaux, France. 8. INSERM French Clinical Research Infrastructure Network, Innovative Clinical Research Network in Vaccinology, France9Collège des Universitaires des Maladies Infectieuses et Tropicales, Paris, France. 9. INSERM French Clinical Research Infrastructure Network, Innovative Clinical Research Network in Vaccinology, France10CHU and UMR 1347, Université de Bourgogne, Dijon, France. 10. Sorbonne Universités, Université Pierre-et-Marie-Curie, Université Paris 06, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique (Unité Mixte de Recherche en Santé 1136), Paris, France11AP-HP, Hôpital Saint Antoine, Unité de Santé Publique.
Abstract
IMPORTANCE: Data on long-term immune responses to hepatitis B virus (HBV) vaccination in adults with human immunodeficiency virus 1 (HIV-1) infection are scarce. OBJECTIVE: To compare long-term (up to month 42) immune responses to the standard HBV vaccination regimen with a 4-injection intramuscular double-dose regimen and a 4-injection intradermal low-dose regimen. DESIGN, SETTING, AND PARTICIPANTS: The phase 3, open-label, multicenter parallel-group (1:1:1 allocation ratio) randomized clinical trial was conducted from June 28, 2007, to October 23, 2008, at 33 centers in France. Participants included 437 HBV-seronegative adults with HIV-1 and CD4 cell counts of more than 200/μL. Follow-up was extended to September 12, 2012, and data were assessed from February 13, 2015, to January 22, 2016. The analysis was imputed for an intention-to-treat population. INTERVENTIONS: Patients were randomly assigned to receive 3 intramuscular standard-dose (20-μg) injections of recombinant HBV vaccine at weeks 0, 4, and 24 (IM20 × 3 group) (145 participants), 4 intramuscular double-dose (40-μg) injections at weeks 0, 4, 8, and 24 (IM40 × 4 group) (148 participants), or 4 intradermal low-dose (4-μg) injections at weeks 0, 4, 8, and 24 (ID4 × 4 group) (144 participants). MAIN OUTCOMES AND MEASURES: The previously published primary trial end point was the percentage of responders at week 28, defined as patients with hepatitis B surface antibody (HBsAb) levels of at least 10 mIU/mL among patients who received at least 1 vaccine dose. The secondary trial end points included the percentage of responders at months 18, 30, and 42 and the duration of response from week 28. Multiple imputation was used to address missing measurements during the follow-up. RESULTS: Among the 437 patients randomized, 426 received at least 1 dose ofvaccine. Of these, 287 were men (67.4%) and they had a mean (SD) age of 42.9 (9.7) years. The percentage of responders at month 42 was 41% (95% CI, 33%-49%) in the IM20 × 3 group, 71% (95% CI, 64%-79%) in the IM40 × 4 group (P < .001 vs the IM20 × 3 group), and 44% (95% CI, 35%-53%) in the ID4 × 4 group (P = .64 vs IM20 × 3 group). Fifteen percent of the patients had HBsAb titers of less than 10 mIU/mL at 33.1 months in the IM40 × 4 group, 8.7 months in the IM20 × 3 group, and 6.8 months in the ID4 × 4 group. CONCLUSIONS AND RELEVANCE: In this follow-up of a trial of adults with HIV-1 infection, the IM40 × 4 regimen ofrecombinant HBV vaccine improved long-term immune response compared with the standard regimen. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00480792.
RCT Entities:
IMPORTANCE: Data on long-term immune responses to hepatitis B virus (HBV) vaccination in adults with human immunodeficiency virus 1 (HIV-1) infection are scarce. OBJECTIVE: To compare long-term (up to month 42) immune responses to the standard HBV vaccination regimen with a 4-injection intramuscular double-dose regimen and a 4-injection intradermal low-dose regimen. DESIGN, SETTING, AND PARTICIPANTS: The phase 3, open-label, multicenter parallel-group (1:1:1 allocation ratio) randomized clinical trial was conducted from June 28, 2007, to October 23, 2008, at 33 centers in France. Participants included 437 HBV-seronegative adults with HIV-1 and CD4 cell counts of more than 200/μL. Follow-up was extended to September 12, 2012, and data were assessed from February 13, 2015, to January 22, 2016. The analysis was imputed for an intention-to-treat population. INTERVENTIONS:Patients were randomly assigned to receive 3 intramuscular standard-dose (20-μg) injections of recombinant HBV vaccine at weeks 0, 4, and 24 (IM20 × 3 group) (145 participants), 4 intramuscular double-dose (40-μg) injections at weeks 0, 4, 8, and 24 (IM40 × 4 group) (148 participants), or 4 intradermal low-dose (4-μg) injections at weeks 0, 4, 8, and 24 (ID4 × 4 group) (144 participants). MAIN OUTCOMES AND MEASURES: The previously published primary trial end point was the percentage of responders at week 28, defined as patients with hepatitis B surface antibody (HBsAb) levels of at least 10 mIU/mL among patients who received at least 1 vaccine dose. The secondary trial end points included the percentage of responders at months 18, 30, and 42 and the duration of response from week 28. Multiple imputation was used to address missing measurements during the follow-up. RESULTS: Among the 437 patients randomized, 426 received at least 1 dose of vaccine. Of these, 287 were men (67.4%) and they had a mean (SD) age of 42.9 (9.7) years. The percentage of responders at month 42 was 41% (95% CI, 33%-49%) in the IM20 × 3 group, 71% (95% CI, 64%-79%) in the IM40 × 4 group (P < .001 vs the IM20 × 3 group), and 44% (95% CI, 35%-53%) in the ID4 × 4 group (P = .64 vs IM20 × 3 group). Fifteen percent of the patients had HBsAb titers of less than 10 mIU/mL at 33.1 months in the IM40 × 4 group, 8.7 months in the IM20 × 3 group, and 6.8 months in the ID4 × 4 group. CONCLUSIONS AND RELEVANCE: In this follow-up of a trial of adults with HIV-1 infection, the IM40 × 4 regimen of recombinant HBV vaccine improved long-term immune response compared with the standard regimen. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00480792.
Authors: E Seremba; P Ocama; R Ssekitoleko; H Mayanja-Kizza; S V Adams; J Orem; E Katabira; S J Reynolds; R Nabatanzi; C Casper; W Phipps Journal: Vaccine Date: 2021-01-28 Impact factor: 3.641
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