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

Joshua A. Horwitz, Ariel Halper-Stromberg, Hugo Mouquet, Alexander D. Gitlin, Anna Tretiakova, Thomas R. Eisenreich, Marine Malbec, Sophia Gravemann, Eva K. Billerbeck, Marcus Dorner, Hildegard Büning, Olivier Schwartz, Elena Knops, Rolf Kaiser, Michael S. Seaman, James M. Wilson, Charles M. Rice, Alexander Ploss, Pamela J. Bjorkman, Florian Klein & 1 others Michel C. Nussenzweig

Research output: Contribution to journalArticle

159 Citations (Scopus)

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load by coadministration of ART and immunotherapy enabled prolonged viremic control by a single bNAb after ART was withdrawn.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.

Original languageEnglish (US)
Pages (from-to)16538-16543
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number41
DOIs
StatePublished - Oct 8 2013
Externally publishedYes

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Neutralizing Antibodies
HIV-1
Viral Load
Immunotherapy
Pharmaceutical Preparations
Viremia
Therapeutics
Dependovirus
DNA
Combination Drug Therapy
HIV Infections
Injections

Keywords

  • CD4bs
  • Glycan
  • Gp160

ASJC Scopus subject areas

  • General

Cite this

HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice. / Horwitz, Joshua A.; Halper-Stromberg, Ariel; Mouquet, Hugo; Gitlin, Alexander D.; Tretiakova, Anna; Eisenreich, Thomas R.; Malbec, Marine; Gravemann, Sophia; Billerbeck, Eva K.; Dorner, Marcus; Büning, Hildegard; Schwartz, Olivier; Knops, Elena; Kaiser, Rolf; Seaman, Michael S.; Wilson, James M.; Rice, Charles M.; Ploss, Alexander; Bjorkman, Pamela J.; Klein, Florian; Nussenzweig, Michel C.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 41, 08.10.2013, p. 16538-16543.

Research output: Contribution to journalArticle

Horwitz, JA, Halper-Stromberg, A, Mouquet, H, Gitlin, AD, Tretiakova, A, Eisenreich, TR, Malbec, M, Gravemann, S, Billerbeck, EK, Dorner, M, Büning, H, Schwartz, O, Knops, E, Kaiser, R, Seaman, MS, Wilson, JM, Rice, CM, Ploss, A, Bjorkman, PJ, Klein, F & Nussenzweig, MC 2013, '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, vol. 110, no. 41, pp. 16538-16543. https://doi.org/10.1073/pnas.1315295110
Horwitz, Joshua A. ; Halper-Stromberg, Ariel ; Mouquet, Hugo ; Gitlin, Alexander D. ; Tretiakova, Anna ; Eisenreich, Thomas R. ; Malbec, Marine ; Gravemann, Sophia ; Billerbeck, Eva K. ; Dorner, Marcus ; Büning, Hildegard ; Schwartz, Olivier ; Knops, Elena ; Kaiser, Rolf ; Seaman, Michael S. ; Wilson, James M. ; Rice, Charles M. ; Ploss, Alexander ; Bjorkman, Pamela J. ; Klein, Florian ; Nussenzweig, Michel C. / HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice. In: Proceedings of the National Academy of Sciences of the United States of America. 2013 ; Vol. 110, No. 41. pp. 16538-16543.
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