by Carolyn Chu, MD, MSc, AAHIVS, AAHIVM Chief Medical Officer
April 11, 2023
Marks KM, Kang M, Umbleja R, et al. Immunogenicity and safety of Hepatitis B vaccine with a Toll-like Receptor 9 Agonist Adjuvant (HEPLISAV-B) in HBV Vaccine-naïve People with HIV. Clin Infect Dis. 2023 Apr 5; ciad201. PMID: 37017075.
ACTG A5379 (BEe-HIVe) is an international, multicenter open-label study examining use of a recombinant HBsAg vaccine adjuvanted with CpG 1018 (HepB-CpG) in people with HIV who were non-responders to prior HBV vaccination (Group A) and people with HIV who have no known prior HBV vaccination (Group B). This study describes Group B seroprotective humoral responses and safety outcomes. The study enrolled adults with negative HBsAg, anti-HBc, and anti-HBs; on ART with CD4 ≥ 100 cells/mm3 and HIV-1 RNA < 1000 copies/mL; and no co-occurring chronic kidney disease stage G4/G5, cancer diagnosis within the previous five years (except resolved Kaposi Sarcoma and designated skin cancers), use of immunosuppressive agents, and pregnancy or breastfeeding. Three doses of HepB-CpG were administered at Weeks 0, 4, and 24; serum anti-HBs measurements were taken at each study visit. Out of 75 participants, 68 had complete data for analysis: all 68 (100%) achieved seroprotection at 4 weeks after the 3-dose vaccine series, and of these 88% had anti-HBs > 1000 mIU/mL. The seroprotection rate was 98.5% at Week 24, prior to the 3rd dose. One or more related adverse events were experienced by 61% – the highest was Grade 1 in 39%, Grade 2 in 20%, and Grade 3 malaise in one participant. Vaccination site pain (40%), malaise (26%), fatigue (23%), myalgia (22%) and headache (22%) were the most common. Post-vaccine fever occurred in 3%. All participants who experienced an adverse event subsequently reported recovery/resolution.
The Hepatitis B Virus Infection section of the DHHS Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV indicates that if a two-dose HBV vaccine is preferred, HepB-CpG is an option (CIII). For this investigation, a 3-dose schedule was selected due to “known challenges with HBV vaccination response in PWH”. Although 100% seroprotection was achieved 4 weeks after three doses of HepB-CpG, 98.5% had seroprotective titers after two doses, a response similar to that observed in registrational trials which utilized a 2-dose schedule in immunocompetent adults. Authors note that certain populations, such as people with chronic kidney disease, may benefit from additional doses of HepB-CpG. Further, while anti-HBs ≥ 10 mIU/mL is the generally recognized correlate for seroprotection, the antibody level achieved is associated with duration of maintenance of antibody titers above the seroprotective threshold (and therefore higher peak antibody levels may be desired). Group B participants are being followed to determine the durability of response after 3 doses.
The author has no conflicts of interest to disclose.
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