Evaluating the Safety, Pharmacokinetics, and Antiviral Activity of a Human Monoclonal Antibody (VRC01) in HIV-Infected Adults Undergoing a Brief Treatment Interruption

Summary

The purpose of this study was to evaluate the safety, tolerability, pharmacokinetics (PK), and antiviral activity of an antibody (called VRC01) in HIV-infected adults whose HIV was well-controlled with HIV medicines. The study examined whether VRC01 controlled or delayed the return of HIV viremia when the participants' HIV medicines were briefly stopped during the study.

Timeline

Start

2015-08

Primary completion

2016-03

Completion

2016-10

Publications

• Background Zhou T, Georgiev I, Wu X, Yang ZY, Dai K, Finzi A, Kwon YD, Scheid JF, Shi W, Xu L, Yang Y, Zhu J, Nussenzweig MC, Sodroski J, Shapiro L, Nabel GJ, Mascola JR, Kwong PD. Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science. 2010 Aug 13;329(5993):811-7. doi: 10.1126/science.1192819. Epub 2010 Jul 8.
• Background Li Y, O'Dell S, Walker LM, Wu X, Guenaga J, Feng Y, Schmidt SD, McKee K, Louder MK, Ledgerwood JE, Graham BS, Haynes BF, Burton DR, Wyatt RT, Mascola JR. Mechanism of neutralization by the broadly neutralizing HIV-1 monoclonal antibody VRC01. J Virol. 2011 Sep;85(17):8954-67. doi: 10.1128/JVI.00754-11. Epub 2011 Jun 29.
• Background U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS. Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0. [November 2014]. Available from: http://rsc.tech-res.com/docs/default-source/safety/daids_ae_grading_table_v2_nov2014.pdf
• Background Manual for Expedited Reporting of Adverse Events to DAIDS, Version 2.0, January 2010.
• Results Bar KJ, Sneller MC, Harrison LJ, Justement JS, Overton ET, Petrone ME, Salantes DB, Seamon CA, Scheinfeld B, Kwan RW, Learn GH, Proschan MA, Kreider EF, Blazkova J, Bardsley M, Refsland EW, Messer M, Clarridge KE, Tustin NB, Madden PJ, Oden K, O'Dell SJ, Jarocki B, Shiakolas AR, Tressler RL, Doria-Rose NA, Bailer RT, Ledgerwood JE, Capparelli EV, Lynch RM, Graham BS, Moir S, Koup RA, Mascola JR, Hoxie JA, Fauci AS, Tebas P, Chun TW. Effect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption. N Engl J Med. 2016 Nov 24;375(21):2037-2050. doi: 10.1056/NEJMoa1608243. Epub 2016 Nov 9.
• Weir IR, Harrison LJ. An evaluation of confidence intervals for a cumulative proportion to enable decisions at interim reviews of single-arm trials. Contemp Clin Trials. 2024 Mar;138:107453. doi: 10.1016/j.cct.2024.107453. Epub 2024 Jan 20.
• Salantes DB, Zheng Y, Mampe F, Srivastava T, Beg S, Lai J, Li JZ, Tressler RL, Koup RA, Hoxie J, Abdel-Mohsen M, Sherrill-Mix S, McCormick K, Overton ET, Bushman FD, Learn GH, Siliciano RF, Siliciano JM, Tebas P, Bar KJ. HIV-1 latent reservoir size and diversity are stable following brief treatment interruption. J Clin Invest. 2018 Jul 2;128(7):3102-3115. doi: 10.1172/JCI120194. Epub 2018 Jun 18.

Drugs

Indications