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Prolonged viral suppression with anti-HIV-1 antibody therapy
被引:0
|作者:
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
Michel C. Nussenzweig
机构:
[1] The Rockefeller University,Laboratory of Molecular Immunology
[2] Columbia University Irving Medical Center,Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center
[3] Harvard Medical School,Labcorp
[4] LabCorp,Monogram Biosciences
[5] The Rockefeller University,Center for Clinical and Translational Science
[6] Massachusetts General Hospital,Division of Infectious Diseases
[7] Massachusetts General Hospital,Division of Gastroenterology
[8] MIT and Harvard,Ragon Institute of MGH
[9] National Institute of Allergy and Infectious Diseases (NIAID),Laboratory of Immunoregulation
[10] National Institutes of Health (NIH),Howard Hughes Medical Institute
[11] The Rockefeller University,undefined
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摘要:
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.
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页码:368 / 374
页数:6
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