b-enhancement of hbv vaccination in persons living with hiv (bee-hive): evaluation of heplisav-b

Conditions: HIV Infection; Hepatitis B

Summary: 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.

Eligibility criteria:
inclusion criteria, groups a and b * hiv-1 infection * on current hiv-1 antiretroviral therapy (art) * cd4+ t-cell count ≥100 cells/mm\^3 * hiv-1 rna \<1000 copies/ml inclusion criteria, group a only * serum hepatitis b antibody \<10 mlu/ml, non-reactive (negative), or indeterminate * documentation of hbv vaccination \>168 days prior to study entry inclusion criterion, group b only * serum hepatitis b antibody non-reactive (negative) within 45 days prior to study entry exclusion criteria, groups a and b * infection or prior exposure to hbv * serum hbsab level ≥10 mlu/ml or positive at screening or any other time prior to screening * presence of any active or acute aids-defining opportunistic infections * solid organ transplantation * history of ascites, encephalopathy, or variceal hemorrhage * diagnosis of chronic kidney disease (ckd) stage g4 * cancer diagnosis within 5 years * currently receiving chemotherapy * chronic use and/or receipt of systemically administered immunosuppressive * known allergy/sensitivity or any hypersensitivity to any hbv vaccine or yeast * active, serious infection other than hiv-1 * receipt of any inactivated virus vaccine within 14 days * receipt of any of the following within 45 days prior to study entry: * live virus vaccine * granulocyte colony-stimulating factor (g-csf) or granulocyte-macrophage colony-stimulating factor (gm-csf) * any other investigational medicinal agent * receipt of immunoglobulin or blood products within 90 days prior to study entry * receipt of an injection of dna plasmids or oligonucleotides within 60 days prior to study entry exclusion criteria, group a only * hepatitis b virus vaccination ≤168 days prior to study entry * receipt of heplisav-b vaccine at any time prior to study entry exclusion criterion, group b only * known hbv vaccination prior to study entry