CD4 Count and CD4/CD8 Ratio Impact Antibody Responses to COVID-19 mRNA Booster Vaccination in People with HIV on Suppressive ART

Objective: To evaluate the durability of SARS-CoV-2–specific humoral and cellular immune responses after booster vaccination in people living with HIV (PLWH) in a prospective longitudinal cohort study. Methods: We analyzed 46 PLWH with no prior history of SARS-CoV-2 infection who received a booster dose. Anti-receptor-binding domain (RBD) IgG concentrations, neutralization titers, and T cell responses were measured over time. The associations between CD4+ T cell count and CD4/CD8 ratio with antibody dynamics were assessed, adjusting for age, sex, and vaccine type. Results: Anti-RBD IgG and neutralization titers declined significantly over time. Participants with CD4+ T cell counts <500 cells/μL exhibited a 3-fold faster decline in anti-RBD IgG compared to those with ≥500 cells/μL. Neutralization capacity declined similarly across both groups, suggesting that CD4+ T cell count primarily influences antibody quantity rather than functional quality. A lower CD4/CD8 ratio was independently associated with reduced baseline IgG concentrations but did not influence the rate of antibody decay. In a subset of 30 participants, a lower CD4/CD8 ratio was also associated with altered follicular helper (Tfh) CD4+ T cell frequencies and faster decline of Spike-specific Tfh over time. Conclusions: CD4+ T cell count influences antibody persistence, while the CD4/CD8 ratio affects initial antibody magnitude and Tfh cell frequencies, highlighting complementary roles in shaping vaccine responses in PLWH.