While vaccination is the cornerstone of prevention strategies for HBV, the response to current standard vaccination is suboptimal in those living with HIV. Hepatitis B vaccination response to standard regimens is suboptimal in persons living with HIV. A variety of modalities to improve response (primary or secondary series) have been utilized but none have gained universal acceptance. Recently, a new vaccine for HBV prevention was approved by the United States (US) Food and Drug Administration (FDA). The HEPLISAV-B® vaccine (Dynavax Technologies Corporation) is a 0.5 mL aqueous mixture of the HBsAg (20 mcg) combined with 3 mg of CpG1018, an adjuvant Toll-like receptor 9 (TLR9) agonist. It is given as an intramuscular (IM) injection at 0 and 1 months. In pivotal trials this regimen was superior to a three-dose vaccine series of ENGERIX-B, which has been licensed and used for many years in the US and worldwide. The proposed study will compare the efficacy and safety of HEPLISAV-B and ENGERIX- B in a population of HBV vaccine non-responders living with HIV. In Kenya, ENGERIX-B vaccine is the currently approved and registered Hepatitis B vaccine, while HEPLISAV-B is not yet registered. This is a is a phase III/IV, prospective, open-label, interventional, two group study being conducted at both US and non-US sites, with one group (Group A) consisting of a randomized, controlled trial with three study arms and the other group (Group B) consisting of a single arm. The study will involve adults living with HIV with a history of nonresponse to hepatitis B (HBV) vaccination (Group A HBV vaccine-experienced) and adults living with HIV with no known prior history of HBV vaccination (Group B HBV vaccine-naïve). Participants in Group A will be randomized 1:1:1 to receive HEPLISAV-B (Arms 1 [two doses] and 2 [three doses]) or ENGERIX-B (Arm 3 [three doses]). Participants in Group B will receive HEPLISAV-B. The study will compare the week 12 seroprotection of a two-dose regimen of HEPLISAV-B (Group A, Arm 1) versus the week 28  seroprotection of a standard three-dose regimen of ENGERIX- B (Group A, Arm 3) in hepatitis B virus (HBV) vaccine-experienced participants living with HIV (Group A).