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Antibody Responses After BA.5/BF.7 Breakthrough Infection in People Living with HIV
Ying Liu1, Zhaowei Guo2, Zhuo Yang2
1Clinical Center for HIV/AIDS, Beijing Ditan Hospital, Beijing 100015, China.
Vaccines
|April 27, 2026
Summary
People living with HIV (PLWH) on suppressive antiretroviral therapy (ART) can develop robust hybrid immunity after COVID-19 vaccination and breakthrough infection. This immunity, comparable to HIV-negative individuals, highlights vaccination
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- People living with HIV (PLWH) are a vulnerable population during the COVID-19 pandemic.
- The immune competence of PLWH on long-term suppressive antiretroviral therapy (ART) to support hybrid immunity remains unclear.
- Functional antibody responses against evolving Omicron subvariants in PLWH are poorly characterized.
Purpose of the Study:
- To assess functional antibody responses in vaccinated and unvaccinated PLWH with breakthrough Omicron subvariant infection.
- To compare antibody neutralization and Fc effector functions in different cohorts.
- To evaluate the impact of ART on hybrid immunity development in PLWH.
Main Methods:
- Three cohorts were enrolled: HIV-negative individuals with breakthrough infection (BTI-HC), vaccinated PLWH with breakthrough infection (BTI-HIV), and unvaccinated PLWH with primary infection (PI-HIV).
- Participants received suppressive ART based on non-nucleoside reverse transcriptase inhibitors or integrase strand transfer inhibitors.
- Measurements included receptor-binding domain (RBD)-specific IgG, neutralizing antibody titers against multiple SARS-CoV-2 variants, and antibody-dependent cellular cytotoxicity (ADCC) responses.
Main Results:
- BTI-HIV participants demonstrated comparable RBD-binding IgG, neutralizing antibody, and ADCC responses to BTI-HC, significantly exceeding PI-HIV.
- Immunological imprinting was observed in breakthrough infection cohorts, with higher neutralizing titers against ancestral D614G than infecting BA.4/5 or BF.7 variants.
- Emerging variants XDV, KP.2, and KP.3 showed substantial neutralization escape across all groups; PI-HIV exhibited diminished neutralization breadth.
Conclusions:
- Suppressive ART enables PLWH to achieve hybrid immunity with neutralizing and ADCC responses comparable to HIV-negative individuals.
- Vaccination is critical for establishing effective hybrid immunity in PLWH, significantly outperforming primary infection in unvaccinated individuals.
- Immunological imprinting and neutralization escape by emerging variants necessitate updated vaccines for HIV-positive populations.
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