OBJECTIVES: To investigate immunogenicity of SARS-CoV-2 vaccine third booster (3BD; fifth dose) with bivalent vaccine original/BA4/5 vaccine in people living with HIV (PLWH). STUDY DESIGN: This is an observational cohort study to evaluate the outcomes of SARS-CoV-2 vaccination (HIV-VAC study). We analyzed microneutralization assay and IFN-γ production in 48 PLWH on ART with CD4 count <200 cell/mm3 and/or previous AIDS according to immunization status: vaccinated PLWH who had a previous SARS-CoV-2 infection (hybrid immunization, HI) vs. those only vaccinated (non-hybrid immunization, nHI) and current CD4 count RESULTS: After 15 days from its administration (T1), the 3BD bivalent mRNA vaccine elicited a statistically significant increase of neutralizing antibodies (nAbs) geometric mean titers (GMTs) from T0 to T1 against W-D614G (fold-increase 4.8; p<0.0001), BA.5 (8.6 p<0.0001), BQ.1.1 (6.4, p<0.0001) and XBB.1 (6.5, p<0.0001). When compared to BA.5, nAbs GMTs against BQ.1.1 and XBB.1 decreased by 3.5 and 4.1-fold, respectively. After controlling for age, years from AIDS diagnosis, CD4 count at administration and CD4 count nadir, the fold change reduction in nAbs response to other VoCs as compared to BA.1, was larger in participants with HI vs. those nHI: 0.59 lower (95%CI 0.36, 0.97, p=0.04) for BQ.1.1 and 0.67 lower (95% CI: 0.47, 0.96, p=0.03) for XBB.1.In contrast, the analysis carried little evidence for an association between current CD4 count and response to the fifth dose of bivalent vaccine. Furthermore, cell-mediated immunity remained stable. CONCLUSIONS: Our data support the current recommendation of offering bivalent mRNA vaccine booster doses to PLWH with low CD4 count or previous AIDS at first vaccination, especially in those who never previously acquired SARS CoV2 and regardless of current CD4 count
