Characteristics of humoral and T-cell immune responses in people living with HIV after breakthrough SARS-CoV-2 Omicron variant infection during December 2022 to January 2023.

Due to inherent immune deficiency, the characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immune responses in people living with HIV (PLWH) following breakthrough infection with remain incompletely elucidated. A large-sample real-world study was conducted from December 2022 to January 2023, which systematically analyzed immune responses in 1,367 PLWH and 219 people without HIV (PWOH) by evaluating serum IgG antibody levels against SARS-CoV-2 wild-type strain and Omicron variants, neutralizing antibody titers, as well as the features of SARS-CoV-2-specific T-cell responses in this population. The results demonstrated that the breakthrough Omicron infection rate in PLWH (60.6%) was significantly lower than that in PWOH. Meanwhile, PLWH exhibited notably reduced IgG antibody levels against both the wild-type strain and Omicron BF.7 variant, with a concurrent decline in neutralizing antibody titers. However, fully vaccinated PLWH with CD4+ T-cell counts ≥ 200 cells/μL achieved post-infection antibody levels comparable to those of PWOH. Notably, PLWH with CD4+ T-cell counts < 200 cells/μL or unvaccinated PLWH showed obvious impairment in both humoral and cellular immunity. Although PLWH could maintain relatively high levels of SARS-CoV-2-specific antibodies and T-cell responses within six months after infection, the overall intensity of their immune responses remained lower than that of PWOH. Furthermore, while wild-type SARS-CoV-2 vaccines could effectively elevate antibody levels in PLWH, their protective efficacy against Omicron variants was relatively limited. These findings provide important experimental and clinical evidence for formulating exclusive and targeted SARS-CoV-2 vaccination strategies for the PLWH.