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J Exp Med. 2018 Sep 3;215(9):2311-2324. doi: 10.1084/jem.20180936. Epub 2018 Aug 2.

Relationship between latent and rebound viruses in a clinical trial of anti-HIV-1 antibody 3BNC117.

Author information

1
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY.
2
Department of Physics and Astronomy, University of California, Riverside, CA.
3
Division of Infectious Diseases, Weill Cornell Medicine, New York, NY.
4
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA.
5
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY mcaskey@rockefeller.edu.
6
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY nussen@rockefeller.edu.
7
Howard Hughes Medical Institute, Chevy Chase, MD.

Abstract

A clinical trial was performed to evaluate 3BNC117, a potent anti-HIV-1 antibody, in infected individuals during suppressive antiretroviral therapy and subsequent analytical treatment interruption (ATI). The circulating reservoir was evaluated by quantitative and qualitative viral outgrowth assay (Q2VOA) at entry and after 6 mo. There were no significant quantitative changes in the size of the reservoir before ATI, and the composition of circulating reservoir clones varied in a manner that did not correlate with 3BNC117 sensitivity. 3BNC117 binding site amino acid variants found in rebound viruses preexisted in the latent reservoir. However, only 3 of 217 rebound viruses were identical to 868 latent viruses isolated by Q2VOA and near full-length sequencing. Instead, 63% of the rebound viruses appeared to be recombinants, even in individuals with 3BNC117-resistant reservoir viruses. In conclusion, viruses emerging during ATI in individuals treated with 3BNC117 are not the dominant species found in the circulating latent reservoir, but frequently appear to represent recombinants of latent viruses.

PMID:
30072495
PMCID:
PMC6122972
DOI:
10.1084/jem.20180936
[Indexed for MEDLINE]
Free PMC Article

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