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

作者：Joshua A. Horwitz, Ariel Halper-Stromberg, Hugo Mouquet, Alexander D. Gitlin, Anna Tretiakova, Thomas Eisenreich, Marine Malbec, Sophia Gravemann, Eva Billerbeck, Marcus Dorner, Hildegard Büning, Olivier Schwartz, Elena Knops, Rolf Kaiser, Michael S. Seaman, James M. Wilson, Charles M. Rice, Alexander Ploß, Pamela J. Björkman, Florian Klein, Michel C. Nussenzweig · 发表于：Proceedings of the National Academy of Sciences · 年份：2013 · DOI：10.1073/pnas.1315295110 · 被引用次数：277 · 研究领域：HIV Research and Treatment、Immune Cell Function and Interaction、Herpesvirus Infections and Treatments

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load by coadministration of ART and immunotherapy enabled prolonged viremic control by a single bNAb after ART was withdrawn.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