SARS-CoV-2 variant specific protective immunity and long-term immune recovery in people living with HIV: a retrospective cohort study

Objectives Effective cross-variant immunity is critical for people living with HIV (PLWH) exposed to evolving SARS-CoV-2 strains. This study investigated variant-specific humoral immune responses and their association with disease progression among PLWH following Omicron BA.5.2/BF.7 breakthrough infection. Methods A total of 455 PLWH and 91 people without HIV (PWOH) were recruited during the Omicron BA.5.2/BF.7 outbreak in China, with peripheral blood samples collected 3–6 months post-infection, followed by a one-year clinical follow-up. Neutralizing antibody (NAb) levels against 19 SARS-CoV-2 variants were measured using a multiplex bead-based flow cytometry assay. Results In the overall cohort, PLWH generated broadly reactive NAbs, but at lower levels than PWOH with matched infection and vaccination status. Wild-type vaccination enhanced NAbs against pre-Omicron and early-Omicron variants, but neutralizing activity against late-Omicron variants remained weak. Serotype analysis confirmed that PLWH with CD4 + T-cell counts < 350 cells/μL exhibited lower NAb titers and diversity, and the JN.1 variant displayed a distinct serotype prior to its global outbreak. Baseline NAb levels against late Omicron variants predicted CD4+ T-cell recovery at one-year follow-up. Conclusions These results provide experimental evidence that may inform the clinical management of PLWH during future SARS-CoV-2 variant outbreaks and provide insights into the predictive value of neutralizing antibodies for long-term immune recovery.