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Nat Commun
. 2024 Mar 15;15(1):2360.
doi: 10.1038/s41467-024-46673-2. Clearance of persistent SARS-CoV-2 associates with increased neutralizing antibodies in advanced HIV disease post-ART initiation
Farina Karim 1 2 , Catherine Riou 3 4 , Mallory Bernstein 1 , Zesuliwe Jule 1 , Gila Lustig 5 , Strauss van Graan 6 7 , Roanne S Keeton 3 , Janine-Lee Upton 1 , Yashica Ganga 1 , Khadija Khan 1 2 , Kajal Reedoy 1 , Matilda Mazibuko 1 , Katya Govender 1 , Kershnee Thambu 1 , Nokuthula Ngcobo 1 , Elizabeth Venter 6 7 , Zanele Makhado 6 7 , Willem Hanekom 1 8 , Anne von Gottberg 9 10 , Monjurul Hoque 11 , Quarraisha Abdool Karim 5 12 , Salim S Abdool Karim 5 12 , Nithendra Manickchund 13 , Nombulelo Magula 14 , Bernadett I Gosnell 13 , Richard J Lessells 5 15 , Penny L Moore 6 7 , Wendy A Burgers 3 4 , Tulio de Oliveira 5 15 16 17 , Mahomed-Yunus S Moosa 13 , Alex Sigal 18 19 20
Affiliations
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.
. 2024 Mar 15;15(1):2360.
doi: 10.1038/s41467-024-46673-2. Clearance of persistent SARS-CoV-2 associates with increased neutralizing antibodies in advanced HIV disease post-ART initiation
Farina Karim 1 2 , Catherine Riou 3 4 , Mallory Bernstein 1 , Zesuliwe Jule 1 , Gila Lustig 5 , Strauss van Graan 6 7 , Roanne S Keeton 3 , Janine-Lee Upton 1 , Yashica Ganga 1 , Khadija Khan 1 2 , Kajal Reedoy 1 , Matilda Mazibuko 1 , Katya Govender 1 , Kershnee Thambu 1 , Nokuthula Ngcobo 1 , Elizabeth Venter 6 7 , Zanele Makhado 6 7 , Willem Hanekom 1 8 , Anne von Gottberg 9 10 , Monjurul Hoque 11 , Quarraisha Abdool Karim 5 12 , Salim S Abdool Karim 5 12 , Nithendra Manickchund 13 , Nombulelo Magula 14 , Bernadett I Gosnell 13 , Richard J Lessells 5 15 , Penny L Moore 6 7 , Wendy A Burgers 3 4 , Tulio de Oliveira 5 15 16 17 , Mahomed-Yunus S Moosa 13 , Alex Sigal 18 19 20
Affiliations
- PMID: 38491050
- PMCID: PMC10943233
- DOI: 10.1038/s41467-024-46673-2
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.