| Title: |
Randomized Clinical Trial to Assess the Impact of the Broadly Neutralizing HIV-1 Monoclonal Antibody VRC01 on HIV-1 Persistence in Individuals on Effective ART |
| Authors: |
Riddler, Sharon A; Zheng, Lu; Durand, Christine M; Ritz, Justin; Koup, Richard A; Ledgerwood, Julie; Bailer, Robert T; Koletar, Susan L; Eron, Joseph J; Keefer, Michael C; Macatangay, Bernard J C; Cyktor, Joshua C; Mellors, John W; Hite, Mark; Clark, Jan; Currin, David; Tipton, Mandy; Weinman, Renee; Onesi, Sara; Hurley, Christine; Bunce, Catherine A; Storey, Sheryl; Dunaway, Shelia; Lambert, Nina; Berzins, Baiba; Gottesman, Joan; Leonard, Michael; Ray, Graham; Kittelson, Pat; Benson, Connie; Muttera, Leticia; Flynn, Teri; Sbrolla, Amy; Wiggins, Ilene; Howard, Jamilla; Arduino, Roberto C; Villamil, Aristoteles E; Kessels, Lisa; Spitz, Teresa; Campbell, Danielle; Kudumu, Mwenda; Sise, Thucuma; Nair, Apsara; Baer, Jenifer; Epperson, Kim; Perelson, Alan; Jennings, Cheryl; Tressler, Randall; Acosta, Ed; Casazza, Joseph |
| Contributors: |
National Institutes of Health; Johns Hopkins University |
| Source: |
Open Forum Infectious Diseases ; volume 5, issue 10 ; ISSN 2328-8957 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2018 |
| Description: |
Background Broadly neutralizing monoclonal antibodies (bnMAbs) may promote clearance of HIV-1-expressing cells through antibody-dependent cell-mediated cytotoxicity. We evaluated the effect of the CD4-binding site bnMAb, VRC01, on measures of HIV-1 persistence in chronically infected individuals. Methods A5342 was a phase 1, randomized, double-blind, placebo-controlled, parallel-arm study. Participants on effective antiretroviral therapy (ART) were randomized to receive 2 infusions of VRC01 (40 mg/kg) at entry and week 3, and 2 infusions of placebo (saline) at weeks 6 and 9; or 2 infusions of placebo at entry and week 3, and 2 infusions of VRC01 at weeks 6 and 9. Results Infusion of VRC01 was safe and well tolerated. The median fold-change in the cell-associated HIV-1 RNA/DNA ratio from baseline to week 6 was 1.12 and 0.83 for the VRC01 and placebo arms, respectively, with no significant difference between arms (P = .16). There were no significant differences in the proportions with residual plasma viremia ≥1 copies/mL or in phorbol 12-myristate 13-acetate/ionomycin-induced virus production from CD4+ T cells between arms (both P > .05). Conclusions In individuals with chronic HIV-1 infection on ART, VRC01 infusions were safe and well tolerated but did not affect plasma viremia, cellular HIV-1 RNA/DNA levels, or stimulated virus production from CD4+ T cells. ClinicalTrials.gov Identifier NCT02411539 |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/ofid/ofy242 |
| Availability: |
https://doi.org/10.1093/ofid/ofy242; http://academic.oup.com/ofid/article-pdf/5/10/ofy242/33577988/ofy242.pdf |
| Rights: |
http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.D489AB73 |
| Database: |
BASE |