Longitudinal assessment of COVID-19 vaccine immunogenicity in people with HIV stratified by CD4+ T-cell count in the Netherlands: A two-year follow-up study

Although guidelines for COVID-19 additional vaccination strategies generally prioritise people with advanced HIV infection, recommendations vary globally, with some countries recommending an annual vaccination for all people with HIV (PWH), while others restrict this to PWH with a CD4+ T-cell count ...

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Veröffentlicht in:	PloS one Jg. 20; H. 5; S. e0323792
Hauptverfasser:	Jongkees, Marlou J., Bogers, Susanne, de Vries, Rory D., GeurtsvanKessel, Corine H., Miranda Afonso, Pedro, Hensley, Kathryn S., Rijnders, Bart J. A., Brinkman, Kees, Rokx, Casper, Roukens, Anna H. E.
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States Public Library of Science 01.01.2025 Public Library of Science (PLoS)
Schlagworte:	Adult Antibodies Antibodies, Viral - blood Antibodies, Viral - immunology Antigens Biology and Life Sciences BNT162 Vaccine - immunology CD4 antigen CD4 Lymphocyte Count CD4-Positive T-Lymphocytes - immunology Clinical trials COVID-19 COVID-19 - epidemiology COVID-19 - immunology COVID-19 - prevention & control COVID-19 vaccines COVID-19 Vaccines - administration & dosage COVID-19 Vaccines - immunology Female Follow-Up Studies Guidelines HIV HIV Infections - immunology Human immunodeficiency virus Humans IgG antibody Immune response Immunogenicity Immunogenicity, Vaccine Immunoglobulin G Immunoglobulin G - blood Immunoglobulin G - immunology Infections Kinetics Longitudinal Studies Lymphocytes T Male Medicine and Health Sciences Middle Aged mRNA Netherlands - epidemiology Prospective Studies Public health SARS-CoV-2 - immunology Severe acute respiratory syndrome coronavirus 2 Spike Glycoprotein, Coronavirus - immunology Vaccination Vaccines Netherlands
ISSN:	1932-6203, 1932-6203
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Abstract	Although guidelines for COVID-19 additional vaccination strategies generally prioritise people with advanced HIV infection, recommendations vary globally, with some countries recommending an annual vaccination for all people with HIV (PWH), while others restrict this to PWH with a CD4+ T-cell count < 200 cells per µL. We conducted a prospective cohort study in 448 adult PWH. The primary outcome was the SARS-CoV-2 spike (S1)-specific IgG antibody level at 1, 6, 12, 18, and 24 months after completing a primary COVID-19 vaccination series (two doses of BNT162b2, mRNA-1273, or ChAdOx1-S, or one dose of Ad26.COV2.S). We compared the antibody kinetics over two years between PWH with a baseline CD4+ T-cell count < 200 cells per µL (n = 16) vs. ≥ 200 cells per µL (n = 432) with a mixed-effects model. Secondary outcomes included variables associated with the kinetics of S1-specific antibody levels and the incidence of breakthrough infections. The median most recent CD4+ T-cell count prior to primary vaccination was 140 (IQR 80-165) in the < 200 cells per µL group, and 688 (IQR 520-899) in the ≥ 200 cells per µL group at the time of primary vaccination. S1-specific antibodies were lower in PWH with a CD4+ T-cell count < 200 vs. ≥ 200 cells per µL during the two-year follow-up, with predicted S1-specific antibody levels of 514 (95% CI 456-578) vs. 2758 (95% CI 1488-5110) BAU per mL at 12 months (p < 0.001) and 839 (95% CI 732-959) vs. 3505 (95% CI 1712-7175) BAU per mL at 24 months (p < 0.001). The overall incidence of SARS-CoV-2 infections was 55% and comparable between groups. A CD4+ T-cell count < 200 cells per µL, higher age, and a vector-based primary vaccination series were negatively associated with S1-specific antibody levels over time. Long-term humoral responses were lower in PWH with a CD4+ T-cell count < 200 cells per µL compared to those with a CD4+ T-cell count ≥ 200 cells per µL. National COVID-19 vaccine guidelines recommending booster vaccines for all PWH, should therefore specifically emphasise the need for booster vaccines in those with a CD4+ T-cell count < 200 cells per µL. Trial registration: The trial was registered on the International Clinical Trials Platform (registration number: EUCTR2021-001054-57-N).
AbstractList	BackgroundAlthough guidelines for COVID-19 additional vaccination strategies generally prioritise people with advanced HIV infection, recommendations vary globally, with some countries recommending an annual vaccination for all people with HIV (PWH), while others restrict this to PWH with a CD4+ T-cell count < 200 cells per µL.MethodsWe conducted a prospective cohort study in 448 adult PWH. The primary outcome was the SARS-CoV-2 spike (S1)-specific IgG antibody level at 1, 6, 12, 18, and 24 months after completing a primary COVID-19 vaccination series (two doses of BNT162b2, mRNA-1273, or ChAdOx1-S, or one dose of Ad26.COV2.S). We compared the antibody kinetics over two years between PWH with a baseline CD4+ T-cell count < 200 cells per µL (n = 16) vs. ≥ 200 cells per µL (n = 432) with a mixed-effects model. Secondary outcomes included variables associated with the kinetics of S1-specific antibody levels and the incidence of breakthrough infections.ResultsThe median most recent CD4+ T-cell count prior to primary vaccination was 140 (IQR 80–165) in the < 200 cells per µL group, and 688 (IQR 520–899) in the ≥ 200 cells per µL group at the time of primary vaccination. S1-specific antibodies were lower in PWH with a CD4+ T-cell count < 200 vs. ≥ 200 cells per µL during the two-year follow-up, with predicted S1-specific antibody levels of 514 (95% CI 456–578) vs. 2758 (95% CI 1488–5110) BAU per mL at 12 months (p < 0.001) and 839 (95% CI 732–959) vs. 3505 (95% CI 1712–7175) BAU per mL at 24 months (p < 0.001). The overall incidence of SARS-CoV-2 infections was 55% and comparable between groups. A CD4+ T-cell count < 200 cells per µL, higher age, and a vector-based primary vaccination series were negatively associated with S1-specific antibody levels over time.ConclusionLong-term humoral responses were lower in PWH with a CD4+ T-cell count < 200 cells per µL compared to those with a CD4+ T-cell count ≥ 200 cells per µL. National COVID-19 vaccine guidelines recommending booster vaccines for all PWH, should therefore specifically emphasise the need for booster vaccines in those with a CD4+ T-cell count < 200 cells per µL.Trial registration: The trial was registered on the International Clinical Trials Platform (registration number: EUCTR2021-001054-57-N). Although guidelines for COVID-19 additional vaccination strategies generally prioritise people with advanced HIV infection, recommendations vary globally, with some countries recommending an annual vaccination for all people with HIV (PWH), while others restrict this to PWH with a CD4+ T-cell count < 200 cells per µL. We conducted a prospective cohort study in 448 adult PWH. The primary outcome was the SARS-CoV-2 spike (S1)-specific IgG antibody level at 1, 6, 12, 18, and 24 months after completing a primary COVID-19 vaccination series (two doses of BNT162b2, mRNA-1273, or ChAdOx1-S, or one dose of Ad26.COV2.S). We compared the antibody kinetics over two years between PWH with a baseline CD4+ T-cell count < 200 cells per µL (n = 16) vs. ≥ 200 cells per µL (n = 432) with a mixed-effects model. Secondary outcomes included variables associated with the kinetics of S1-specific antibody levels and the incidence of breakthrough infections. The median most recent CD4+ T-cell count prior to primary vaccination was 140 (IQR 80-165) in the < 200 cells per µL group, and 688 (IQR 520-899) in the ≥ 200 cells per µL group at the time of primary vaccination. S1-specific antibodies were lower in PWH with a CD4+ T-cell count < 200 vs. ≥ 200 cells per µL during the two-year follow-up, with predicted S1-specific antibody levels of 514 (95% CI 456-578) vs. 2758 (95% CI 1488-5110) BAU per mL at 12 months (p < 0.001) and 839 (95% CI 732-959) vs. 3505 (95% CI 1712-7175) BAU per mL at 24 months (p < 0.001). The overall incidence of SARS-CoV-2 infections was 55% and comparable between groups. A CD4+ T-cell count < 200 cells per µL, higher age, and a vector-based primary vaccination series were negatively associated with S1-specific antibody levels over time. Long-term humoral responses were lower in PWH with a CD4+ T-cell count < 200 cells per µL compared to those with a CD4+ T-cell count ≥ 200 cells per µL. National COVID-19 vaccine guidelines recommending booster vaccines for all PWH, should therefore specifically emphasise the need for booster vaccines in those with a CD4+ T-cell count < 200 cells per µL. Trial registration: The trial was registered on the International Clinical Trials Platform (registration number: EUCTR2021-001054-57-N). Although guidelines for COVID-19 additional vaccination strategies generally prioritise people with advanced HIV infection, recommendations vary globally, with some countries recommending an annual vaccination for all people with HIV (PWH), while others restrict this to PWH with a CD4+ T-cell count < 200 cells per µL.BACKGROUNDAlthough guidelines for COVID-19 additional vaccination strategies generally prioritise people with advanced HIV infection, recommendations vary globally, with some countries recommending an annual vaccination for all people with HIV (PWH), while others restrict this to PWH with a CD4+ T-cell count < 200 cells per µL.We conducted a prospective cohort study in 448 adult PWH. The primary outcome was the SARS-CoV-2 spike (S1)-specific IgG antibody level at 1, 6, 12, 18, and 24 months after completing a primary COVID-19 vaccination series (two doses of BNT162b2, mRNA-1273, or ChAdOx1-S, or one dose of Ad26.COV2.S). We compared the antibody kinetics over two years between PWH with a baseline CD4+ T-cell count < 200 cells per µL (n = 16) vs. ≥ 200 cells per µL (n = 432) with a mixed-effects model. Secondary outcomes included variables associated with the kinetics of S1-specific antibody levels and the incidence of breakthrough infections.METHODSWe conducted a prospective cohort study in 448 adult PWH. The primary outcome was the SARS-CoV-2 spike (S1)-specific IgG antibody level at 1, 6, 12, 18, and 24 months after completing a primary COVID-19 vaccination series (two doses of BNT162b2, mRNA-1273, or ChAdOx1-S, or one dose of Ad26.COV2.S). We compared the antibody kinetics over two years between PWH with a baseline CD4+ T-cell count < 200 cells per µL (n = 16) vs. ≥ 200 cells per µL (n = 432) with a mixed-effects model. Secondary outcomes included variables associated with the kinetics of S1-specific antibody levels and the incidence of breakthrough infections.The median most recent CD4+ T-cell count prior to primary vaccination was 140 (IQR 80-165) in the < 200 cells per µL group, and 688 (IQR 520-899) in the ≥ 200 cells per µL group at the time of primary vaccination. S1-specific antibodies were lower in PWH with a CD4+ T-cell count < 200 vs. ≥ 200 cells per µL during the two-year follow-up, with predicted S1-specific antibody levels of 514 (95% CI 456-578) vs. 2758 (95% CI 1488-5110) BAU per mL at 12 months (p < 0.001) and 839 (95% CI 732-959) vs. 3505 (95% CI 1712-7175) BAU per mL at 24 months (p < 0.001). The overall incidence of SARS-CoV-2 infections was 55% and comparable between groups. A CD4+ T-cell count < 200 cells per µL, higher age, and a vector-based primary vaccination series were negatively associated with S1-specific antibody levels over time.RESULTSThe median most recent CD4+ T-cell count prior to primary vaccination was 140 (IQR 80-165) in the < 200 cells per µL group, and 688 (IQR 520-899) in the ≥ 200 cells per µL group at the time of primary vaccination. S1-specific antibodies were lower in PWH with a CD4+ T-cell count < 200 vs. ≥ 200 cells per µL during the two-year follow-up, with predicted S1-specific antibody levels of 514 (95% CI 456-578) vs. 2758 (95% CI 1488-5110) BAU per mL at 12 months (p < 0.001) and 839 (95% CI 732-959) vs. 3505 (95% CI 1712-7175) BAU per mL at 24 months (p < 0.001). The overall incidence of SARS-CoV-2 infections was 55% and comparable between groups. A CD4+ T-cell count < 200 cells per µL, higher age, and a vector-based primary vaccination series were negatively associated with S1-specific antibody levels over time.Long-term humoral responses were lower in PWH with a CD4+ T-cell count < 200 cells per µL compared to those with a CD4+ T-cell count ≥ 200 cells per µL. National COVID-19 vaccine guidelines recommending booster vaccines for all PWH, should therefore specifically emphasise the need for booster vaccines in those with a CD4+ T-cell count < 200 cells per µL. Trial registration: The trial was registered on the International Clinical Trials Platform (registration number: EUCTR2021-001054-57-N).CONCLUSIONLong-term humoral responses were lower in PWH with a CD4+ T-cell count < 200 cells per µL compared to those with a CD4+ T-cell count ≥ 200 cells per µL. National COVID-19 vaccine guidelines recommending booster vaccines for all PWH, should therefore specifically emphasise the need for booster vaccines in those with a CD4+ T-cell count < 200 cells per µL. Trial registration: The trial was registered on the International Clinical Trials Platform (registration number: EUCTR2021-001054-57-N). Background Although guidelines for COVID-19 additional vaccination strategies generally prioritise people with advanced HIV infection, recommendations vary globally, with some countries recommending an annual vaccination for all people with HIV (PWH), while others restrict this to PWH with a CD4 + T-cell count < 200 cells per µL. Methods We conducted a prospective cohort study in 448 adult PWH. The primary outcome was the SARS-CoV-2 spike (S1)-specific IgG antibody level at 1, 6, 12, 18, and 24 months after completing a primary COVID-19 vaccination series (two doses of BNT162b2, mRNA-1273, or ChAdOx1-S, or one dose of Ad26.COV2.S). We compared the antibody kinetics over two years between PWH with a baseline CD4 + T-cell count < 200 cells per µL (n = 16) vs. ≥ 200 cells per µL (n = 432) with a mixed-effects model. Secondary outcomes included variables associated with the kinetics of S1-specific antibody levels and the incidence of breakthrough infections. Results The median most recent CD4 + T-cell count prior to primary vaccination was 140 (IQR 80–165) in the < 200 cells per µL group, and 688 (IQR 520–899) in the ≥ 200 cells per µL group at the time of primary vaccination. S1-specific antibodies were lower in PWH with a CD4 + T-cell count < 200 vs. ≥ 200 cells per µL during the two-year follow-up, with predicted S1-specific antibody levels of 514 (95% CI 456–578) vs. 2758 (95% CI 1488–5110) BAU per mL at 12 months (p < 0.001) and 839 (95% CI 732–959) vs. 3505 (95% CI 1712–7175) BAU per mL at 24 months (p < 0.001). The overall incidence of SARS-CoV-2 infections was 55% and comparable between groups. A CD4 + T-cell count < 200 cells per µL, higher age, and a vector-based primary vaccination series were negatively associated with S1-specific antibody levels over time. Conclusion Long-term humoral responses were lower in PWH with a CD4 + T-cell count < 200 cells per µL compared to those with a CD4 + T-cell count ≥ 200 cells per µL. National COVID-19 vaccine guidelines recommending booster vaccines for all PWH, should therefore specifically emphasise the need for booster vaccines in those with a CD4 + T-cell count < 200 cells per µL. Trial registration: The trial was registered on the International Clinical Trials Platform (registration number: EUCTR2021-001054-57-N).
Author	Hensley, Kathryn S. Bogers, Susanne de Vries, Rory D. Rokx, Casper Roukens, Anna H. E. Brinkman, Kees Rijnders, Bart J. A. GeurtsvanKessel, Corine H. Jongkees, Marlou J. Miranda Afonso, Pedro
AuthorAffiliation	3 Department of Biostatistics, Erasmus University Medical Centre, Rotterdam, The Netherlands 5 Department of Internal Medicine and Infectious Diseases, OLVG Hospital, Amsterdam, The Netherlands 6 Department of Infectious Diseases, Leiden University Medical Centre, Leiden, The Netherlands PLOS: Public Library of Science, UNITED STATES OF AMERICA 1 Department of Internal Medicine, Section Infectious Diseases, and Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Centre, Rotterdam, The Netherlands 4 Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, The Netherlands 2 Department of Viroscience, Erasmus University Medical Centre, Rotterdam, The Netherlands
AuthorAffiliation_xml	– name: 1 Department of Internal Medicine, Section Infectious Diseases, and Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Centre, Rotterdam, The Netherlands – name: PLOS: Public Library of Science, UNITED STATES OF AMERICA – name: 4 Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, The Netherlands – name: 2 Department of Viroscience, Erasmus University Medical Centre, Rotterdam, The Netherlands – name: 3 Department of Biostatistics, Erasmus University Medical Centre, Rotterdam, The Netherlands – name: 5 Department of Internal Medicine and Infectious Diseases, OLVG Hospital, Amsterdam, The Netherlands – name: 6 Department of Infectious Diseases, Leiden University Medical Centre, Leiden, The Netherlands
Author_xml	– sequence: 1 givenname: Marlou J. orcidid: 0000-0002-9589-7281 surname: Jongkees fullname: Jongkees, Marlou J. – sequence: 2 givenname: Susanne surname: Bogers fullname: Bogers, Susanne – sequence: 3 givenname: Rory D. surname: de Vries fullname: de Vries, Rory D. – sequence: 4 givenname: Corine H. surname: GeurtsvanKessel fullname: GeurtsvanKessel, Corine H. – sequence: 5 givenname: Pedro orcidid: 0000-0001-6708-9597 surname: Miranda Afonso fullname: Miranda Afonso, Pedro – sequence: 6 givenname: Kathryn S. orcidid: 0000-0003-1675-2445 surname: Hensley fullname: Hensley, Kathryn S. – sequence: 7 givenname: Bart J. A. surname: Rijnders fullname: Rijnders, Bart J. A. – sequence: 8 givenname: Kees surname: Brinkman fullname: Brinkman, Kees – sequence: 9 givenname: Casper surname: Rokx fullname: Rokx, Casper – sequence: 10 givenname: Anna H. E. orcidid: 0000-0002-1397-0992 surname: Roukens fullname: Roukens, Anna H. E.
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/40388467$$D View this record in MEDLINE/PubMed
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Copyright_xml	– notice: Copyright: © 2025 Jongkees et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. – notice: 2025 Jongkees et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. – notice: 2025 Jongkees et al 2025 Jongkees et al – notice: 2025 Jongkees et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
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DocumentTitleAlternate	Two-year follow-up of COVID-19 vaccine immunogenicity in people with HIV stratified by CD4+ T-cell count
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License	Copyright: © 2025 Jongkees et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Creative Commons Attribution License
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Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: RDdV is supported by the Health~Holland grant EMCLHS20017, co-funded by the PPP Allowance made available by the Health~Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships, and is listed as an inventor of the fusion inhibitory lipopeptide [SARSHRCPEG4]2-chol in a provisional patent application. KSH has received support for attending meetings and travel from Gilead. BJAR declares the receipt of research grants from Gilead and MSD and honoraria for advisory boards from AstraZeneca, Roche, Gilead, and F2G. KB has received research and educational grants from ViiV and Gilead, as well as consulting fees for advisory boards from ViiV, Gilead, MSD, and AstraZeneca. CR has received research grants from ViiV, Gilead, ZonMW, AIDSfonds, Erasmus MC, and Health~Holland, and honoraria for advisory boards from Gilead and ViiV. AR has received grants from the Bill and Melinda Gates Foundation and the Leids Universitair Fonds, participated on the board of an investor-initiated clinical trial on convalescent plasma for COVID-19, and is the chief editor of the Dutch Journal of Infectious Diseases and a member of the European Medicines Agency expert group on vaccines. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The other authors have declared that no competing interests exist.
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Snippet	Although guidelines for COVID-19 additional vaccination strategies generally prioritise people with advanced HIV infection, recommendations vary globally, with... BackgroundAlthough guidelines for COVID-19 additional vaccination strategies generally prioritise people with advanced HIV infection, recommendations vary... Background Although guidelines for COVID-19 additional vaccination strategies generally prioritise people with advanced HIV infection, recommendations vary...
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Title	Longitudinal assessment of COVID-19 vaccine immunogenicity in people with HIV stratified by CD4+ T-cell count in the Netherlands: A two-year follow-up study
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