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

TitleRelationship between latent and rebound viruses in a clinical trial of anti-HIV-1 antibody 3BNC117.
Publication TypeJournal Article
Year of Publication2018
AuthorsCohen YZ, Lorenzi JCC, Krassnig L, Barton JP, Burke L, Pai J, Lu C-L, Mendoza P, Oliveira TY, Sleckman C, Millard K, Butler AL, Dizon JP, Belblidia SA, Witmer-Pack M, Shimeliovich I, Gulick RM, Seaman MS, Jankovic M, Caskey M, Nussenzweig MC
JournalJ Exp Med
Volume215
Issue9
Pagination2311-2324
Date Published09/03/2018
ISSN1540-9538
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 (QVOA) 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 QVOA 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.

DOI10.1084/jem.20180936
Alternate JournalJ. Exp. Med.
PubMed ID30072495
PubMed Central IDPMC6122972
Grant ListUM1 AI126620 / AI / NIAID NIH HHS / United States
UL1 TR000043 / TR / NCATS NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
P30 AI124414 / AI / NIAID NIH HHS / United States
U01 AI118536 / AI / NIAID NIH HHS / United States
KL2 TR001865 / TR / NCATS NIH HHS / United States
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