Background
A5379 primary analysis demonstrated that 2- and 3-dose HepB-CpG (2-CpG, 3-CpG) achieved superior seroprotective response (SPR defined as anti-HBs ≥10 mIU/mL) compared to 3-dose HepB-alum (3-alum) in PWH with prior HBV vaccine non-response (Group A), and 100% SPR was achieved with 3-CpG in vaccine-naïve PWH (Group B). SPR durability is now evaluated.
Methods
A5379 evaluated immunogenicity of HepB-CpG in PWH on ART with CD4 ≥100 cells/mm3 and HIV-1 RNA <1000 copies/mL. Group A was randomized 1:1:1 to: 2-CpG intramuscularly (IM) (20 mcg recombinant HBsAg, 3000 mcg CpG 1018® adjuvant) at Wks 0 and 4; 3-CpG IM at Wks 0, 4, 24; or 3-alum IM (20 mcg recombinant HBsAg) at Wks 0, 4, 24. All Group B participants received 3-CpG. End of study anti-HBs was assessed at Wk72 (48 wks after 3-dose, 68 wks after 2-dose) regardless of visit window. SPR proportion differences in Group A were estimated with two-sided 97.5% Newcombe CI, stratified by sex at birth and diabetes status. Otherwise, 95% Wilson CIs were used.
Results
Group A included 561 participants at 41 sites in 10 countries and Group B 74 participants at 13 sites in 3 countries. 95% of Group A and 100% of Group B completed study follow-up to Wk72.
Group A: At end of study, 86.1% of 2-CpG (n=173), 97.2% of 3-CpG (n=177), and 57.5% of 3-alum (n=174) had SPR. SPR% difference was 28.6% (18.0%,38.4%) for 2-CPG v. 3-alum, 39.2% (30.0%,47.9%) for 3-CpG v. 3-alum, and 11.0% (4.3%,18.1%) for 3-CpG v. 2-CpG. The proportion who achieved SPR at any time on study but had anti-HBs <10 mIU/mL by study end was 2.1% for 3-CpG, 10.7% for 2-CpG and 22.0% in 3-alum. Among those with anti-HBs >1000 mIU/mL at the primary vaccine response time (Wk28 for 3-dose arms and Wk12 for 2-dose), 100% in all arms had SPR at study end. Overall, 73.3% (66.5%,79.1%), 77.7% (71.2%,83.0%), and 73.7% (66.9%,79.5%) of participants in 2-CpG, 3-CpG, and 3-alum reported AEs; two deaths unrelated to vaccines (TB, Wk43 2-CpG; and cardiac arrest, Wk36 3-CpG).
Group B: At the end of study, 97.3% (90.7%,99.3%) of 74 participants had SPR. The 2 participants with anti-HBs <10 mIU/mL were among those with the lowest anti-HBs titers at time of primary vaccine response time. 87.8% (78.5%, 93.5%) reported AEs; no deaths.
Conclusions
In PWH, higher end of study seroprotection was achieved with HepB-CpG over HepB-alum, and 3 doses of HepB-CpG over 2 doses. HepB-CpG achieved durable seroprotection in both vaccine-naïve and prior vaccine non-response groups.