The purpose of this study is to evaluate response to and safety of the HBV vaccine HEPLISAV-B in two study populations living with HIV: prior HBV vaccine recipients who are deemed non-responders and individuals who are naïve to HBV vaccination.
This phase III/IV study will evaluate the response to and safety of the HBV vaccine HEPLISAV-B in two study populations living with HIV: prior HBV vaccine recipients who are deemed non-responders (Group A) and individuals who are naïve to HBV vaccination (Group B). Group A (HBV vaccine non-responders) The study is designed as an open-label three-arm study to evaluate whether: 1. HEPLISAV-B vaccination given as a two-dose series achieves non-inferior seroprotection response (SPR) compared to standard dose ENGERIX-B. 2. HEPLISAV-B vaccination given as a three-dose series achieves superior SPR proportion compared to standard dose ENGERIX-B. Participants are randomized in 1:1:1 ratio to the following study arms, stratified by sex at birth (male vs. female) and diabetes diagnosis status (yes vs. no): - Arm 1: Two doses of HEPLISAV-B at weeks 0 and 4. - Arm 2: Three doses of HEPLISAV-B at weeks 0, 4, and 24. - Arm 3: Three doses of ENGERIX-B at weeks 0, 4, and 24. The target sample size in Group A is 561 participants, 187 participants in each arm. Group B (Naïve to HBV vaccination) Group B study is a single arm evaluation of vaccine response and safety of three doses of HEPLISAV-B. The target sample size is 73 participants. All participants will remain on their non-study-provided antiretroviral therapy (ART) throughout the study. Participants in both groups will attend several study visits through Week 72. Visits may include physical examinations and blood collection. For 7 days after each vaccination, participants will record temperature and any reactions they have to the vaccine.