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Relationship between latent and rebound viruses in a clinical trial of anti-HIV-1 antibody 3BNC117.
- Source :
-
The Journal of experimental medicine [J Exp Med] 2018 Sep 03; Vol. 215 (9), pp. 2311-2324. Date of Electronic Publication: 2018 Aug 02. - Publication Year :
- 2018
-
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 (Q <superscript>2</superscript> VOA) 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 Q <superscript>2</superscript> VOA 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.<br /> (© 2018 Cohen et al.)
- Subjects :
- Adolescent
Adult
Aged
Anti-Retroviral Agents immunology
Female
Follow-Up Studies
HIV Antibodies immunology
Humans
Male
Middle Aged
Anti-Retroviral Agents administration & dosage
HIV Antibodies administration & dosage
HIV Infections blood
HIV Infections drug therapy
HIV Infections genetics
HIV Infections immunology
HIV-1 genetics
HIV-1 immunology
Recombination, Genetic drug effects
Recombination, Genetic immunology
Viral Load genetics
Viral Load immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1540-9538
- Volume :
- 215
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- The Journal of experimental medicine
- Publication Type :
- Academic Journal
- Accession number :
- 30072495
- Full Text :
- https://doi.org/10.1084/jem.20180936