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Contributed by Michel C. Nussenzweig, August 14, 2013 (sent for review July 30, 2013)
Significance
Treatment of HIV-1 infection in humans is achieved using combinations of highly effective antiretroviral therapy (ART) drugs to potently suppress viral replication and prevent the emergence of drug-resistant viruses. However, ART drugs must be taken indefinitely owing to rapid return of viremia upon termination of treatment. Highly potent broadly neutralizing antibodies (bNAbs) present a new potential therapeutic modality in the treatment of HIV-1 infection. Because of their comparatively longer half-lives relative to ART drugs and their ability to eliminate infected cells, bNAbs may alleviate some aspects of the lifelong treatment adherence burden of ART. Here we show that lowering the initial viral load with ART enables single bNAbs to effectively control an established HIV-1 infection 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load by coadministration of ART and immunotherapy enabled prolonged viremic control by a single bNAb after ART was withdrawn.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.
Footnotes
↵1F.K. and M.C.N. contributed equally to this work.
- ↵2To whom correspondence should be addressed. E-mail: nussen{at}mail.rockefeller.edu.
Author contributions: J.A.H., O.S., P.J.B., F.K., and M.C.N. designed research; J.A.H., A.H.-S., H.M., A.D.G., T.R.E., M.M., E.B., M.D., E.K., R.K., M.S.S., and F.K. performed research; A.T., S.G., H.B., J.M.W., C.M.R., and A.P. contributed new reagents/analytic tools; J.A.H., A.H.-S., F.K., and M.C.N. analyzed data; and J.A.H. and M.C.N. wrote the paper.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1315295110/-/DCSupplemental.
Durable HIV-1 control by bNAbs after stopping ART
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