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HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption
Open accessAbstract
Interruption of combination antiretroviral therapy (ART) in HIV-1-infected individuals leads to rapid viral rebound. Here we report the results of a phase IIa open label clinical trial evaluating 3BNC117, a broad and potent neutralizing antibody (bNAb) against the CD4 binding site of HIV-1 Env, in the setting of analytical treatment interruption (ATI) in 13 HIV-1-infected individuals. Participants with 3BNC117-sensitive virus outgrowth cultures were enrolled. Two or four 30 mg/kg infusions of 3BNC117, separated by 3 or 2 weeks, respectively, were generally well tolerated. The infusions were associated with a delay in viral rebound for 5-9 weeks after 2 infusions, and up to 19 weeks after 4 infusions, or an average of 6.7 and 9.9 weeks respectively, compared with 2.6 weeks for historical controls (p=<1e-5). Rebound viruses arose predominantly from a single provirus. In most individuals, emerging viruses showed increased resistance indicating escape. However, 30% of participants remained suppressed until antibody concentrations waned below 20 μg/ml, and the viruses emerging in all but one of these individuals showed no apparent resistance to 3BCN117, suggesting failure to escape over a period of 9-19 weeks. We conclude that administration of 3BNC117 exerts strong selective pressure on HIV-1 emerging from latent reservoirs during ATI in humans.
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Metadata
- Authors
- Scheid, J. F., Horwitz, J. A., Bar-On, Y., Kreider, E. F., Lu, C.-L., Lorenzi, J. C. C., Feldmann, A., Braunschweig, M., Nogueira, L., Oliveira, T., Shimeliovich, I., Patel, R., Burke, L., Cohen, Y. Z., Hadrigan, S., Settler, A., Witmer-Pack, M., West, Juelg, B., Keler, T., Hawthorne, T., Zingman, B., Gulick, R. M., Pfeifer, N., Learn, G. H., Seaman, M. S., Bjorkman, P. J., Klein, F., Schlesinger, S. J., Walker, B. D., Hahn, B. H., Nussenzweig, M. C., & Caskey, M.
- Venue
- Nature
- Published
- 2016-06-22
- Volume
- 535
- Issue
- 7613
- Pages
- 556-560
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2473595575
- Cited by
- 472
- References
- 51
- FWCI
- 42.51
- Type
- journal article
- Language
- en
- Open access
- green
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- Scheid, J. F., Horwitz, J. A., Bar-On, Y., Kreider, E. F., Lu, C.-L., Lorenzi, J. C. C., Feldmann, A., Braunschweig, M., Nogueira, L., Oliveira, T., Shimeliovich, I., Patel, R., Burke, L., Cohen, Y. Z., Hadrigan, S., Settler, A., Witmer-Pack, M., West, Juelg, B., . . . Caskey, M. (2016). HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption. Nature. https://doi.org/10.1038/nature18929
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
