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

TY - JOUR

T1 - HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice

AU - Horwitz, Joshua A.

AU - Halper-Stromberg, Ariel

AU - Mouquet, Hugo

AU - Gitlin, Alexander D.

AU - Tretiakova, Anna

AU - Eisenreich, Thomas R.

AU - Malbec, Marine

AU - Gravemann, Sophia

AU - Billerbeck, Eva

AU - Dorner, Marcus

AU - Büning, Hildegard

AU - Schwartz, Olivier

AU - Knops, Elena

AU - Kaiser, Rolf

AU - Seaman, Michael S.

AU - Wilson, James M.

AU - Rice, Charles M.

AU - Ploss, Alexander

AU - Bjorkman, Pamela J.

AU - Klein, Florian

AU - Nussenzweig, Michel C.

PY - 2013/10/8

Y1 - 2013/10/8

N2 - 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load by coadministration of ART and immunotherapy enabled prolonged viremic control by a single bNAb after ART was withdrawn.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.

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load by coadministration of ART and immunotherapy enabled prolonged viremic control by a single bNAb after ART was withdrawn.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

KW - CD4bs

KW - Glycan

KW - Gp160

UR - https://www.scopus.com/pages/publications/84885338257

UR - https://www.scopus.com/pages/publications/84885338257#tab=citedBy

U2 - 10.1073/pnas.1315295110

DO - 10.1073/pnas.1315295110

M3 - Article

C2 - 24043801

SN - 0027-8424

VL - 110

SP - 16538

EP - 16543

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 41

ER -