Effect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption.

TitleEffect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption.
Publication TypeJournal Article
Year of Publication2016
AuthorsBar KJ, Sneller MC, Harrison LJ, J Justement S, Overton ET, Petrone ME, D Salantes B, 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 KS, 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 T-W
JournalN Engl J Med
Volume375
Issue21
Pagination2037-2050
Date Published2016 11 24
ISSN1533-4406
KeywordsAdult, Aged, Antibodies, Monoclonal, Antibodies, Neutralizing, Female, Historically Controlled Study, HIV, HIV Infections, Humans, Male, Middle Aged, Phylogeny, RNA, Viral, Viral Load, Viremia
Abstract

BACKGROUND: The discovery of potent and broadly neutralizing antibodies (bNAbs) against human immunodeficiency virus (HIV) has made passive immunization a potential strategy for the prevention and treatment of HIV infection. We sought to determine whether passive administration of VRC01, a bNAb targeting the HIV CD4-binding site, can safely prevent or delay plasma viral rebound after the discontinuation of antiretroviral therapy (ART).

METHODS: We conducted two open-label trials (AIDS Clinical Trials Group [ACTG] A5340 and National Institutes of Health [NIH] 15-I-0140) of the safety, side-effect profile, pharmacokinetic properties, and antiviral activity of VRC01 in persons with HIV infection who were undergoing interruption of ART.

RESULTS: A total of 24 participants were enrolled, and one serious alcohol-related adverse event occurred. Viral rebound occurred despite plasma VRC01 concentrations greater than 50 μg per milliliter. The median time to rebound was 4 weeks in the A5340 trial and 5.6 weeks in the NIH trial. Study participants were more likely than historical controls to have viral suppression at week 4 (38% vs. 13%, P=0.04 by a two-sided Fisher's exact test in the A5340 trial; and 80% vs. 13%, P<0.001 by a two-sided Fisher's exact test in the NIH trial) but the difference was not significant at week 8. Analyses of virus populations before ART as well as before and after ART interruption showed that VRC01 exerted pressure on rebounding virus, resulting in restriction of recrudescent viruses and selection for preexisting and emerging antibody neutralization-resistant virus.

CONCLUSIONS: VRC01 slightly delayed plasma viral rebound in the trial participants, as compared with historical controls, but it did not maintain viral suppression by week 8. In the small number of participants enrolled in these trials, no safety concerns were identified with passive immunization with a single bNAb (VRC01). (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTG A5340 and NIH 15-I-0140 ClinicalTrials.gov numbers, NCT02463227 and NCT02471326 .).

DOI10.1056/NEJMoa1608243
Alternate JournalN. Engl. J. Med.
PubMed ID27959728
PubMed Central IDPMC5292134
Grant ListUM1 AI126620 / AI / NIAID NIH HHS / United States
P30 AI027767 / AI / NIAID NIH HHS / United States
U01 AI069534 / AI / NIAID NIH HHS / United States
UM1 AI069534 / AI / NIAID NIH HHS / United States
P30 AI045008 / AI / NIAID NIH HHS / United States
R21 AI118431 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069452 / AI / NIAID NIH HHS / United States
F30 AI112426 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States
U01 AI069452 / AI / NIAID NIH HHS / United States
U01 AI032783 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States