Immune Reconstitution and Antigenic Exposure History Shape Virus-Specific Humoral Immunity in People with HIV
CD4+ T-cell recovery is widely used to assess immune reconstitution in people with HIV, but its relationship to virus-specific humoral immunity across pathogens remains unclear. We characterized neutralizing activity against SARS-CoV-2, HIV-1, and influenza viruses in ART-treated, virologically suppressed individuals spanning distinct CD4+ T-cell levels. BA.5 was the dominant SARS-CoV-2…
The study investigates the relationship between immune reconstitution and virus-specific humoral immunity in HIV-positive individuals. It examines neutralizing activity against SARS-CoV-2, HIV-1, and influenza viruses in ART-treated, virologically suppressed people with varying CD4+ T-cell counts. The BA.5 variant emerged as the dominant target for SARS-CoV-2 neutralization across CD4 strata, while the D614G mutation showed increased neutralization with enhanced immune reconstitution.
This gradient was less apparent for antigenically distinct NB.1.8.1 and XFG variants. In contrast, HIV-1 neutralization was inversely linked to CD4+ T-cell count, with influenza exhibiting strain-specific patterns. The findings reveal that immune reconstitution does not uniformly translate into antiviral humoral function. Instead, antibody profiles align with host immune status, prior antigenic exposure, and viral antigenic evolution.
This highlights the need for pathogen-specific functional assessments in addition to conventional immune monitoring.
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