Clearance of persistent SARS-CoV-2 associates with increased neutralizing antibodies in advanced HIV disease post-ART initiation

Farina Karim, Catherine Riou, Mallory Bernstein, Zesuliwe Jule, Gila Lustig, Strauss Graan, Roanne S. Keeton, Janine-Lee Upton, Yashica Ganga, Khadija Khan, Kajal Reedoy, Matilda Mazibuko, Katya Govender, Kershnee Thambu, Nokuthula Ngcobo, Elizabeth Venter, Zanele Makhado, Willem Hanekom, Anne Gottberg, Monjurul Hoque, Quarraisha Abdool Karim, Salim S. Abdool Karim, Nithendra Manickchund, Nombulelo Magula, Bernadett I. Gosnell, Richard J. Lessells, Penny L. Moore, Wendy A. Burgers, Tulio Oliveira, Mahomed-Yunus S. Moosa and Alex Sigal ()
Additional contact information
Farina Karim: Africa Health Research Institute
Catherine Riou: University of Cape Town
Mallory Bernstein: Africa Health Research Institute
Zesuliwe Jule: Africa Health Research Institute
Gila Lustig: Centre for the AIDS Programme of Research in South Africa
Strauss Graan: University of the Witwatersrand
Roanne S. Keeton: University of Cape Town
Janine-Lee Upton: Africa Health Research Institute
Yashica Ganga: Africa Health Research Institute
Khadija Khan: Africa Health Research Institute
Kajal Reedoy: Africa Health Research Institute
Matilda Mazibuko: Africa Health Research Institute
Katya Govender: Africa Health Research Institute
Kershnee Thambu: Africa Health Research Institute
Nokuthula Ngcobo: Africa Health Research Institute
Elizabeth Venter: University of the Witwatersrand
Zanele Makhado: University of the Witwatersrand
Willem Hanekom: Africa Health Research Institute
Anne Gottberg: a division of the National Health Laboratory Service
Monjurul Hoque: KwaDabeka Community Health Centre
Quarraisha Abdool Karim: Centre for the AIDS Programme of Research in South Africa
Salim S. Abdool Karim: Centre for the AIDS Programme of Research in South Africa
Nithendra Manickchund: University of KwaZulu-Natal
Nombulelo Magula: University of Kwa-Zulu Natal
Bernadett I. Gosnell: University of KwaZulu-Natal
Richard J. Lessells: Centre for the AIDS Programme of Research in South Africa
Penny L. Moore: University of the Witwatersrand
Wendy A. Burgers: University of Cape Town
Tulio Oliveira: Centre for the AIDS Programme of Research in South Africa
Mahomed-Yunus S. Moosa: University of KwaZulu-Natal
Alex Sigal: Africa Health Research Institute

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract SARS-CoV-2 clearance requires adaptive immunity but the contribution of neutralizing antibodies and T cells in different immune states is unclear. Here we ask which adaptive immune responses associate with clearance of long-term SARS-CoV-2 infection in HIV-mediated immunosuppression after suppressive antiretroviral therapy (ART) initiation. We assembled a cohort of SARS-CoV-2 infected people in South Africa (n = 994) including participants with advanced HIV disease characterized by immunosuppression due to T cell depletion. Fifty-four percent of participants with advanced HIV disease had prolonged SARS-CoV-2 infection (>1 month). In the five vaccinated participants with advanced HIV disease tested, SARS-CoV-2 clearance associates with emergence of neutralizing antibodies but not SARS-CoV-2 specific CD8 T cells, while CD4 T cell responses were not determined due to low cell numbers. Further, complete HIV suppression is not required for clearance, although it is necessary for an effective vaccine response. Persistent SARS-CoV-2 infection led to SARS-CoV-2 evolution, including virus with extensive neutralization escape in a Delta variant infected participant. The results provide evidence that neutralizing antibodies are required for SARS-CoV-2 clearance in HIV-mediated immunosuppression recovery, and that suppressive ART is necessary to curtail evolution of co-infecting pathogens to reduce individual health consequences as well as public health risk linked with generation of escape mutants.

Date: 2024
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DOI: 10.1038/s41467-024-46673-2

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