Prolonged viral suppression with anti-HIV-1 antibody therapy

Christian Gaebler, Lilian Nogueira, Elina Stoffel, Thiago Y. Oliveira, Gaëlle Breton, Katrina G. Millard, Martina Turroja, Allison Butler, Victor Ramos, Michael S. Seaman, Jacqueline D. Reeves, Christos J. Petroupoulos, Irina Shimeliovich, Anna Gazumyan, Caroline S. Jiang, Nikolaus Jilg, Johannes F. Scheid, Rajesh Gandhi, Bruce D. Walker, Michael C. Sneller, Anthony Fauci, Tae-Wook Chun, Marina Caskey () and Michel C. Nussenzweig ()
Additional contact information
Christian Gaebler: The Rockefeller University
Lilian Nogueira: The Rockefeller University
Elina Stoffel: The Rockefeller University
Thiago Y. Oliveira: The Rockefeller University
Gaëlle Breton: The Rockefeller University
Katrina G. Millard: The Rockefeller University
Martina Turroja: The Rockefeller University
Allison Butler: The Rockefeller University
Victor Ramos: The Rockefeller University
Michael S. Seaman: Harvard Medical School
Jacqueline D. Reeves: LabCorp
Christos J. Petroupoulos: LabCorp
Irina Shimeliovich: The Rockefeller University
Anna Gazumyan: The Rockefeller University
Caroline S. Jiang: The Rockefeller University
Nikolaus Jilg: Massachusetts General Hospital
Johannes F. Scheid: Massachusetts General Hospital
Rajesh Gandhi: Massachusetts General Hospital
Bruce D. Walker: MIT and Harvard
Michael C. Sneller: National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)
Anthony Fauci: National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)
Tae-Wook Chun: National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)
Marina Caskey: The Rockefeller University
Michel C. Nussenzweig: The Rockefeller University

Nature, 2022, vol. 606, issue 7913, 368-374

Abstract: Abstract HIV-1 infection remains a public health problem with no cure. Anti-retroviral therapy (ART) is effective but requires lifelong drug administration owing to a stable reservoir of latent proviruses integrated into the genome of CD4+ T cells1. Immunotherapy with anti-HIV-1 antibodies has the potential to suppress infection and increase the rate of clearance of infected cells2,3. Here we report on a clinical study in which people living with HIV received seven doses of a combination of two broadly neutralizing antibodies over 20 weeks in the presence or absence of ART. Without pre-screening for antibody sensitivity, 76% (13 out of 17) of the volunteers maintained virologic suppression for at least 20 weeks off ART. Post hoc sensitivity analyses were not predictive of the time to viral rebound. Individuals in whom virus remained suppressed for more than 20 weeks showed rebound viraemia after one of the antibodies reached serum concentrations below 10 µg ml−1. Two of the individuals who received all seven antibody doses maintained suppression after one year. Reservoir analysis performed after six months of antibody therapy revealed changes in the size and composition of the intact proviral reservoir. By contrast, there was no measurable decrease in the defective reservoir in the same individuals. These data suggest that antibody administration affects the HIV-1 reservoir, but additional larger and longer studies will be required to define the precise effect of antibody immunotherapy on the reservoir.

Date: 2022
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DOI: 10.1038/s41586-022-04597-1

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