Heterogeneity of baseline immune activation and SARS-CoV-2 vaccine responses in people with HIV: a multicenter prospective study.

OBJECTIVE

The aim of this study was to determine whether baseline immune activation and inflammation contribute to heterogeneity in SARS-CoV-2 vaccine-induced immunity in antiretroviral therapy (ART)-treated people with HIV (PWH) compared to controls.

METHODS

In this multicenter prospective study, 159 ART-treated PWH from two cohorts and 56 HIV-negative controls were enrolled. The two PWH cohorts differed in immunovirological control: one showed sustained viral suppression and CD4 + T-cell recovery, the other persistent CD4 + T-cell lymphopenia despite ART, sometimes with residual viremia. Baseline plasma levels of 20 cytokines, chemokines and soluble endothelial markers, were measured before SARS-CoV-2 mRNA vaccination. Post-vaccination anti-spike IgG, neutralizing antibodies, and IFN-γ-producing T cells were quantified and correlated with baseline immune mediators.

RESULTS

PWH had higher baseline levels of innate immune activation and endothelial inflammation markers than controls, particularly among immunological nonresponders. Principal component analysis identified two inflammatory profile groups among PWH: one characterized by Th1/Th17-oriented cytokine profile, and the other with dominant monocyte activation and endothelial markers. Higher baseline inflammation in PWH was associated with reduced humoral vaccine responses and elevated ICAM-1 levels with decreased IFN-γ T-cell responses, irrespective of prior SARS-CoV-2 infection. In contrast, among HIV-negative participants with prior SARS-CoV-2 exposure, higher sCD14, IL-12p70, MCP-1, and E-selectin levels correlated with stronger humoral responses, whereas ICAM-1 was associated with increased IFN-γ T-cell responses.

CONCLUSION

Baseline inflammatory and endothelial profiles may constitute additional determinants of SARS-CoV-2 vaccine-induced immune responses in PWH. The opposite associations observed in controls highlight the context-dependent immunological effects of these pathways across chronic immune dysfunction and immunocompetent states.