Background:
Conventional Hepatitis B surface antigen (HBsAg)-based vaccines achieve seroprotection response (SPR, HBsAb≥10 mIU/mL) in 35-80% of people with HIV (PWH) with 3 doses. HepB-CpG (vaccine with a TLR-9 agonist adjuvant) achieves high SPR in PWH, but limited data exist for non-responders to conventional vaccines.
Methods:
ACTG A5379 is an ongoing, open-label study to evaluate immunogenicity of HepB-CpG in PWH. Prior vaccine non-responders were on ART with CD4 ≥100 cells/mm3 and HIV-1 RNA <1000 copies/mL without past or present serologic evidence of HBV or HBV vaccine response. Participants were randomized 1:1:1 to: 2 doses of HepB-CpG intramuscularly (IM) (20 mcg recombinant HBsAg, 3000 mcg CpG 1018® adjuvant) at Wks 0 and 4 (2-CpG); 3 doses of HepB-CpG IM at Wks 0, 4, 24 (3-CpG); or 3 doses of HepB-alum IM (20 mcg recombinant HBsAg) at Wks 0, 4, 24 (3-alum). Primary SPR was defined at Wk12 for 2-CpG and Wk28 for 3-CpG and 3-alum. We assessed noninferiority (NI) of 2-CpG vs 3-alum with a 10% margin and superiority of 3-CpG vs 3-alum. Predefined primary analysis set excluded missed sample collection. Safety was also assessed.
Results:
Of the 561 eligible participants enrolled at 41 sites from 10 countries: 64% were male, 42% Black, 35% White, 17% Asian, 22% Hispanic. Median age was 46 years (range 18-70), 56% enrolled in the US, 21% Africa, 17% Asia, 6% S. America. Median CD4 was 638 cells/mm3, 94% had HIV-1 RNA <40 copies/mL, 29% BMI >30, and 13% diabetes. 96% completed all prescribed doses. The analysis included 505 participants (99% of 508 in the primary analysis set). SPR was achieved in 93% of 2-CpG (n=174), 99% of 3-CpG (n=169), and 80% of 3-alum (n=162). SPR difference between 2-CpG and 3-alum was 13% (97.5% CI: 5%, 22%), achieving NI and indicating superiority. SPR of 3-CpG was superior to 3-alum with a difference of 19% (97.5% repeated CI: 11%, 27%). By Wk12, >90% of participants who received HepB-CpG achieved SPR (Figure 1). Three doses of HepB-CpG achieved a higher proportion with titers >1000 mIU/ml compared to two, and to 3 doses of HepB-alum. One or more AEs related to vaccines were experienced by 33%, 45% and 36% of 2-CpG, 3-CpG and 3-alum participants, respectively, mostly Gr 1 and 2. Vaccination site pain, fatigue, headache, malaise and myalgia were most frequent.
Conclusions:
In this study of PWH with prior vaccine non-response, both 2 and 3 doses of HepB-CpG achieved superior SPR compared to 3 doses of HepB-alum. No unexpected safety issues were observed.
