title: HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice.
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load by coadministration of ART and immunotherapy enabled prolonged viremic control by a single bNAb after ART was withdrawn.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.
authors.affiliation: Laboratory of Molecular Immunology, Laboratory of Virology and Infectious Diseases, and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Horwitz
authors.forename: Ariel
authors.initials: A
authors.lastname: Halper-Stromberg
authors.forename: Hugo
authors.initials: H
authors.lastname: Mouquet
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Gitlin
authors.forename: Anna
authors.initials: A
authors.lastname: Tretiakova
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Eisenreich
authors.forename: Marine
authors.initials: M
authors.lastname: Malbec
authors.forename: Sophia
authors.initials: S
authors.lastname: Gravemann
authors.forename: Eva
authors.initials: E
authors.lastname: Billerbeck
authors.forename: Marcus
authors.initials: M
authors.lastname: Dorner
authors.forename: Hildegard
authors.initials: H
authors.lastname: Büning
authors.forename: Olivier
authors.initials: O
authors.lastname: Schwartz
authors.forename: Elena
authors.initials: E
authors.lastname: Knops
authors.forename: Rolf
authors.initials: R
authors.lastname: Kaiser
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.forename: James M
authors.initials: JM
authors.lastname: Wilson
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rice
authors.forename: Alexander
authors.initials: A
authors.lastname: Ploss
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Bjorkman
authors.forename: Florian
authors.initials: F
authors.lastname: Klein
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
mesh_terms: D000818:Animals; D044966:Anti-Retroviral Agents / Q000276:immunology* / Q000494:pharmacology; D057134:Antibodies, Neutralizing / Q000276:immunology* / Q000494:pharmacology; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000378:metabolism; D000229:Dependovirus; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008822:Mice, Transgenic; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D019562:Viral Load / Q000187:drug effects
chemical_list: D044966:Anti-Retroviral Agents; D057134:Antibodies, Neutralizing; D017931:DNA Primers; D004279:DNA, Viral
keywords: CD4bs; glycan; gp160
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