Infusion Reactions After Receiving the Broadly Neutralizing Antibody VRC01 or Placebo to Reduce HIV-1 Acquisition: Results From the Phase 2b Antibody-Mediated Prevention Randomized Trials.
Journal
Journal of acquired immune deficiency syndromes (1999)
ISSN: 1944-7884
Titre abrégé: J Acquir Immune Defic Syndr
Pays: United States
ID NLM: 100892005
Informations de publication
Date de publication:
01 04 2022
01 04 2022
Historique:
received:
18
06
2021
accepted:
29
10
2021
pubmed:
20
12
2021
medline:
9
3
2022
entrez:
19
12
2021
Statut:
ppublish
Résumé
The antibody-mediated prevention (AMP) studies (HVTN 703/HPTN 081 and HVTN 704/HPTN 085) are harmonized phase 2b trials to assess HIV prevention efficacy and safety of intravenous infusion of anti-gp120 broadly neutralizing antibody VRC01. Antibodies for other indications can elicit infusion-related reactions (IRRs), often requiring premedication and limiting their application. We report on AMP study IRRs. From 2016 to 2018, 2699 HIV-uninfected, at-risk men and transgender adults in the Americas and Switzerland (704/085) and 1924 at-risk heterosexual women in sub-Saharan Africa (703/081) were randomized 1:1:1 to VRC01 10 mg/kg, 30 mg/kg, or placebo. Participants received infusions every 8 weeks (n = 10/participant) over 72 weeks, with 104 weeks of follow-up. Safety assessments were conducted before and after infusion and at noninfusion visits. A total of 40,674 infusions were administered. Forty-seven participants (1.7%) experienced 49 IRRs in 704/085; 93 (4.8%) experienced 111 IRRs in 703/081 (P < 0.001). IRRs occurred more frequently in VRC01 than placebo recipients in 703/081 (P < 0.001). IRRs were associated with atopic history (P = 0.046) and with younger age (P = 0.023) in 703/081. Four clinical phenotypes of IRRs were observed: urticaria, dyspnea, dyspnea with rash, and "other." Urticaria was most prevalent, occurring in 25 (0.9%) participants in 704/085 and 41 (2.1%) participants in 703/081. Most IRRs occurred with the initial infusion and incidence diminished through the last infusion. All reactions were managed successfully without sequelae. IRRs in the AMP studies were uncommon, typically mild or moderate, successfully managed at the research clinic, and resolved without sequelae. Analysis is ongoing to explore potential IRR mechanisms.
Sections du résumé
BACKGROUND
The antibody-mediated prevention (AMP) studies (HVTN 703/HPTN 081 and HVTN 704/HPTN 085) are harmonized phase 2b trials to assess HIV prevention efficacy and safety of intravenous infusion of anti-gp120 broadly neutralizing antibody VRC01. Antibodies for other indications can elicit infusion-related reactions (IRRs), often requiring premedication and limiting their application. We report on AMP study IRRs.
METHODS
From 2016 to 2018, 2699 HIV-uninfected, at-risk men and transgender adults in the Americas and Switzerland (704/085) and 1924 at-risk heterosexual women in sub-Saharan Africa (703/081) were randomized 1:1:1 to VRC01 10 mg/kg, 30 mg/kg, or placebo. Participants received infusions every 8 weeks (n = 10/participant) over 72 weeks, with 104 weeks of follow-up. Safety assessments were conducted before and after infusion and at noninfusion visits. A total of 40,674 infusions were administered.
RESULTS
Forty-seven participants (1.7%) experienced 49 IRRs in 704/085; 93 (4.8%) experienced 111 IRRs in 703/081 (P < 0.001). IRRs occurred more frequently in VRC01 than placebo recipients in 703/081 (P < 0.001). IRRs were associated with atopic history (P = 0.046) and with younger age (P = 0.023) in 703/081. Four clinical phenotypes of IRRs were observed: urticaria, dyspnea, dyspnea with rash, and "other." Urticaria was most prevalent, occurring in 25 (0.9%) participants in 704/085 and 41 (2.1%) participants in 703/081. Most IRRs occurred with the initial infusion and incidence diminished through the last infusion. All reactions were managed successfully without sequelae.
CONCLUSIONS
IRRs in the AMP studies were uncommon, typically mild or moderate, successfully managed at the research clinic, and resolved without sequelae. Analysis is ongoing to explore potential IRR mechanisms.
Identifiants
pubmed: 34923559
doi: 10.1097/QAI.0000000000002892
pii: 00126334-202204010-00007
pmc: PMC9555144
mid: NIHMS1764280
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
Broadly Neutralizing Antibodies
0
HIV Antibodies
0
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
405-413Subventions
Organisme : NIAID NIH HHS
ID : UM1 AI069456
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069412
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069469
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068614
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068618
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI154463
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI068635
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068635
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068619
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI068618
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI069412
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI068619
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI068614
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068617
Pays : United States
Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
S.R.W. has received clinical trial funding from Janssen Vaccines. The other authors have no conflicts of interest to disclose.
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