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HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice.

Joshua A Horwitz 1 Ariel Halper-Stromberg 1 Hugo Mouquet 1, 2 Alexander D Gitlin 1 Anna Tretiakova 3 Thomas R Eisenreich 1 Marine Malbec 4 Sophia Gravemann 5 Eva Billerbeck 6 Marcus Dorner 6 Hildegard Büning 5 Olivier Schwartz 4 Elena Knops 5 Rolf Kaiser 5 Michael S Seaman 7 James M Wilson 3 Charles M Rice 6 Alexander Ploss 8, 6 Pamela J Bjorkman 9 Florian Klein 1 Michel C Nussenzweig 1, 10, *
* Corresponding author
1 Laboratory of Molecular Immunology
2 Réponse humorale aux pathogènes
3 Department of Pathology and Laboratory Medicine
4 Virus et Immunité
5 Institute for Virology
6 Laboratory of Virology and Infectious Disease
7 Beth Israel Deaconess Medical Center
8 Department of Molecular Biology
9 Division of Biology and Howard Hughes Medical Institute
10 HHMI - Howard Hughes Medical Institute
Abstract : Effective control of HIV-1 infection in humans is achieved using combinations of antiretroviral therapy (ART) drugs. In humanized mice (hu-mice), control of viremia can be achieved using either ART or by immunotherapy using combinations of broadly neutralizing antibodies (bNAbs). Here we show that treatment of HIV-1-infected hu-mice with a combination of three highly potent bNAbs not only resulted in complete viremic control but also led to a reduction in cell-associated HIV-1 DNA. Moreover, lowering the initial viral load by coadministration of ART and immunotherapy enabled prolonged viremic control by a single bNAb after ART was withdrawn. Similarly, a single injection of adeno-associated virus directing expression of one bNAb produced durable viremic control after ART was terminated. We conclude that immunotherapy reduces plasma viral load and cell-associated HIV-1 DNA and that decreasing the initial viral load enables single bNAbs to control viremia in hu-mice.
Keywords : CD4bs glycan gp160
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Journal articles
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https://hal-pasteur.archives-ouvertes.fr/pasteur-01109449
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Submitted on : Monday, January 26, 2015 - 1:27:02 PM
Last modification on : Friday, July 17, 2020 - 10:56:02 AM

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Joshua A Horwitz, Ariel Halper-Stromberg, Hugo Mouquet, Alexander D Gitlin, Anna Tretiakova, et al.. HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice.. Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2013, 110 (41), pp.16538-43. ⟨10.1073/pnas.1315295110⟩. ⟨pasteur-01109449⟩

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