Strong serological responses and HIV RNA increase following AS03-adjuvanted pandemic immunization in HIV-infected patients

Authors

  • A Calmy,

    Corresponding author
    • Division of Infectious Diseases, HIV Unit, Department of Internal Medicine, University Hospitals of Geneva & Faculty of Medicine, University of Geneva, Geneva, Switzerland
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  • M Bel,

    1. Centre for Vaccinology, Department of Pathology-Immunology and Paediatrics, University Hospitals of Geneva & Faculty of Medicine, University of Geneva, Geneva, Switzerland
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  • A Nguyen,

    1. Division of Infectious Diseases, HIV Unit, Department of Internal Medicine, University Hospitals of Geneva & Faculty of Medicine, University of Geneva, Geneva, Switzerland
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  • C Combescure,

    1. Clinical Research Centre, University Hospitals of Geneva & Faculty of Medicine, University of Geneva, Geneva, Switzerland
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  • C Delhumeau,

    1. Division of Infectious Diseases, HIV Unit, Department of Internal Medicine, University Hospitals of Geneva & Faculty of Medicine, University of Geneva, Geneva, Switzerland
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  • S Meier,

    1. Centre for Vaccinology, Department of Pathology-Immunology and Paediatrics, University Hospitals of Geneva & Faculty of Medicine, University of Geneva, Geneva, Switzerland
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  • S Yerly,

    1. Laboratory of Virology and Swiss National Centre for Influenza, Department of Genetics and Laboratory Medicine, University Hospital & Faculty of Medicine, Geneva, Switzerland
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  • L Kaiser,

    1. Laboratory of Virology and Swiss National Centre for Influenza, Department of Genetics and Laboratory Medicine, University Hospital & Faculty of Medicine, Geneva, Switzerland
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  • B Hirschel,

    1. Division of Infectious Diseases, HIV Unit, Department of Internal Medicine, University Hospitals of Geneva & Faculty of Medicine, University of Geneva, Geneva, Switzerland
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  • C-A Siegrist,

    1. Centre for Vaccinology, Department of Pathology-Immunology and Paediatrics, University Hospitals of Geneva & Faculty of Medicine, University of Geneva, Geneva, Switzerland
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  • the H1N1 study group

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Correspondence: Dr Alexandra Calmy, Division of Infectious Diseases, University Hospitals of Geneva, 4 Rue Gabrielle Perret-Gentil, 1211 Geneva 14, Switzerland. Tel: +4122-3729242, fax: +4122-3729599, e-mail: alexandra.calmy@hcuge.ch

Abstract

Introduction

We aimed to determine the antibody responses and effect on viral load of the AS03-adjuvanted pandemic H1N1 vaccine in HIV-infected patients.

Method

A total of 121 HIV-infected patients and 138 healthy subjects were enrolled in a prospective, open-label study. Healthy subjects received one dose and HIV-infected patients two doses of the AS03-adjuvanted split influenza A/09/H1N1 vaccine (Pandemrix®; GlaxoSmithKline, Brentford, United Kingdom.) at an interval of 3–4 weeks. The study was extended in 2010/2011 for 66 patients. Geometric mean titres (GMTs), seroprotection rates (post-vaccination titre ≥1:40) and HIV-1 RNA levels were measured before and 4 weeks after immunization.

Results

After two immunizations, the seroprotection rate (94.2 vs. 87%, respectively) and GMT (376 vs. 340, respectively) in HIV-infected patients were as high as in healthy subjects after one dose, regardless of CD4 cell count. Four weeks after immunization, HIV RNA was detected in plasma samples from 40 of 68 (58.0%) previously aviraemic patients [median 152 HIV-1 RNA copies/mL; interquartile range (IQR) 87–509 copies/mL]. Subsequent measures indicated that HIV RNA levels had again declined to <20 copies/mL in most patients (27 of 34; 79.4%). Following (nonadjuvanted) influenza immunization in 2010/2011, HIV RNA levels only slightly increased (median final level 28 copies/mL) in three of 66 (4.5%) previously aviraemic patients, including two of 25 (8%) patients in whom an increase had been elicited by AS03-adjuvanted vaccine the year before.

Conclusion

Most HIV-infected patients developed seroprotection after two doses of AS03-adjuvanted pandemic vaccine. A transient effect on HIV RNA levels was observed in previously aviraemic patients. A booster dose of the nonadjuvanted influenza vaccine containing the A/09/H1N1 strain the following year did not reproduce this finding, indicating a non-antigen-specific adjuvant effect.

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