article · Nature Communications
Clearing SARS-CoV-2 requires adaptive immunity, but the relative roles of neutralizing antibodies and T cells during immune recovery have remained unclear. In a study of 994 SARS-CoV-2 infected individuals in South Africa, over half of the participants with advanced HIV disease experienced prolonged infections lasting more than one month. Among evaluated vaccinated participants with advanced HIV, viral clearance correlated with the appearance of neutralizing antibodies rather than specific CD8 T cells. Full HIV suppression was not strictly required to clear the virus, but it was essential for mounting an effective vaccine response. Prolonged infection also drove viral evolution, including the development of extensive neutralization escape variants. Effective antiretroviral therapy is therefore vital to curb the generation of dangerous escape mutants in immunosuppressed populations.
People living with advanced HIV are at high risk of prolonged viral infections, which can worsen personal health and allow viruses to mutate into new variants that escape immune defenses. Demonstrating that antiretroviral therapy and neutralizing antibodies help clear these persistent infections shows how managing HIV protects broader public health from newly emerging viral variants.
This early-stage clinical research could inform targeted therapeutic and vaccination strategies developed by healthcare providers and biopharmaceutical developers. By identifying neutralizing antibodies as key to clearance, the findings could guide antibody-based therapies or tailored vaccine regimens for immunosuppressed patients, though direct clinical applications remain at an early, pre-commercial stage.
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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.
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DOI: 10.1038/s41467-024-46673-2
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