Prolonged viral suppression with anti-HIV-1 antibody therapy

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 cells . Immunotherapy with anti-HIV-1 antibodies has the potential t...

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Bibliographic Details
Published in:Nature (London) 2022-06, Vol.606 (7913), p.368-374
Main Authors: Gaebler, Christian, Nogueira, Lilian, Stoffel, Elina, Oliveira, Thiago Y, Breton, Gaëlle, Millard, Katrina G, Turroja, Martina, Butler, Allison, Ramos, Victor, Seaman, Michael S, Reeves, Jacqueline D, Petroupoulos, Christos J, Shimeliovich, Irina, Gazumyan, Anna, Jiang, Caroline S, Jilg, Nikolaus, Scheid, Johannes F, Gandhi, Rajesh, Walker, Bruce D, Sneller, Michael C, Fauci, Anthony, Chun, Tae-Wook, Caskey, Marina, Nussenzweig, Michel C
Format: Article
Language:English
Subjects:
Anti-Retroviral Agents - therapeutic use
Antibodies
Antiretroviral therapy
Antiviral agents
Blood & organ donations
CD4 antigen
CD4-Positive T-Lymphocytes - virology
Genomes
HIV
HIV Antibodies - therapeutic use
HIV Infections - drug therapy
HIV-1 - drug effects
HIV-1 - growth & development
Human immunodeficiency virus
Humans
Immunotherapy
Infections
Lymphocytes
Proviruses
Proviruses - drug effects
Public health
Sensitivity analysis
Therapy
Viral Load - drug effects
Viremia
Viremia - drug therapy
Virus Latency - drug effects
Viruses
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Summary: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 cells . Immunotherapy with anti-HIV-1 antibodies has the potential to suppress infection and increase the rate of clearance of infected cells . 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 . 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.
ISSN:0028-0836
1476-4687
1476-4687
DOI:10.1038/s41586-022-04597-1