S2666 Seroprotection of Hepb-Alum vs Hepb-Cpg Vaccines in People With HIV: A Meta-Analysis and Systematic Review

Introduction: Patients with HIV are at increased risk of hepatitis B virus (HBV) infection and often show suboptimal response to conventional HBV vaccines. HepB-alum, an aluminum-adjuvanted vaccine, has been widely used but demonstrates limited immunogenicity in immunocompromised hosts. HepB-CpG, which incorporates a Toll-like receptor 9 agonist (CpG 1018) as an adjuvant, has shown superior immunogenicity in the general population and is now being explored in PWH. We conducted a meta-analysis comparing seroprotection rates between HepB-CpG and HepB-alum vaccines in patients with HIV, as well as evaluating factors associated with seroconversion. Methods: A systematic review of MEDLINE, EMBASE, and scopus through May 2025 identified studies comparing seroconversion outcomes between HepB-CpG and HepB-alum in adults with HIV. Two studies met inclusion criteria: one phase 3 randomized trial and one retrospective observational cohort. The primary outcome was the pooled odds ratio (OR) of seroconversion between the 2 vaccine types. Secondary analysis examined demographic and clinical factors associated with successful seroconversion. Pooled ORs were calculated using a random-effects model. Results: Our meta-analysis included 459 participants (224 HepB-alum; 235 HepB-CpG). The pooled odds of achieving seroprotection (defined as HBsAb ≥10 IU/L) were significantly higher with HepB-CpG compared to HepB-alum (OR 5.34; 95% CI: 1.71–16.65; P = 0.004), with moderate heterogeneity (I² = 66%). In subgroup analysis, absence of diabetes was associated with higher seroconversion (84.1%), while rates were comparable in participants with chronic kidney disease, prior use of steroids or biologics. Seroprotection was also consistent across sexes, with 80.8% of men and 87.1% of women achieving response. Conclusion: HepB-CpG offers significantly improved seroprotection over HepB-alum in people with HIV. Clinical factors such as diabetes may impact vaccine responsiveness, but seroconversion remains high across other subgroups including those with CKD or prior immunosuppressive therapy. Given the enhanced efficacy and comparable safety profile, HepB-CpG should be strongly considered in vaccination strategies for persons with HIV. Larger prospective studies are needed to confirm these findings and inform vaccine policy.