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

• Published in: Nature communications 2024-03, Vol.15 (1), p.2360-2360, Article 2360
• Main Authors: Karim, Farina, Riou, Catherine, Bernstein, Mallory, Jule, Zesuliwe, Lustig, Gila, van Graan, Strauss, Keeton, Roanne S., Upton, Janine-Lee, Ganga, Yashica, Khan, Khadija, Reedoy, Kajal, Mazibuko, Matilda, Govender, Katya, Thambu, Kershnee, Ngcobo, Nokuthula, Venter, Elizabeth, Makhado, Zanele, Hanekom, Willem, von Gottberg, Anne, Hoque, Monjurul, Karim, Quarraisha Abdool, Abdool Karim, Salim S., Manickchund, Nithendra, Magula, Nombulelo, Gosnell, Bernadett I., Lessells, Richard J., Moore, Penny L., Burgers, Wendy A., de Oliveira, Tulio, Moosa, Mahomed-Yunus S., Sigal, Alex
• Format: Article
• Language: English
• Subjects: 13; 13/106; 13/109; 13/31; 631/181/2474; 631/250/2152/2153/1291; 631/250/254; 631/250/255/1901; 631/326/596/4130; Adaptive immunity; Antibodies; Antibody response; Antiretroviral agents; Antiretroviral therapy; CD4 antigen; CD8 antigen; Clearances; COVID-19; Evolution; Health risks; HIV; Human immunodeficiency virus; Humanities and Social Sciences; Immune clearance; Immunosuppression; Infections; Lymphocytes; Lymphocytes T; multidisciplinary; Neutralization; Neutralizing; Persistent infection; Public health; Recovery; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Viral diseases
• ISSN: 2041-1723; 2041-1723
• 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. There is limited data on immune factors contributing to SARS-CoV-2 viral clearance in people living with HIV. Here, the authors show that re-emergence of the neutralizing antibody response may be key to clearing persistent SARS-CoV-2 infection in ART-mediated recovery from immunosuppression in advanced HIV disease.