학술논문
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.
Document Type
Academic Journal
Author
Takuva S; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.; Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; School of Health Systems and Public Health, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.; Karuna ST; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.; Juraska M; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.; Rudnicki E; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.; Edupuganti S; Division of Infectious Disease, Department of Medicine, Emory University, Atlanta, GA.; Anderson M; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.; De La Grecca R; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.; Gaudinski MR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.; Sehurutshi A; Botswana Harvard AIDS Institute, Gaborone, Botswana, South Africa.; Orrell C; Department of Medicine, Desmond Tutu HIV Center, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.; Naidoo L; South African Medical Research Council, Durban, South Africa.; Valencia J; Asociacion Civil Impacta Salud y Educacion, Lima, Peru.; Villela LM; Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz (INI-Fiocruz), Rio de Janeiro, Brazil.; Walsh SR; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA.; Andrew P; Family Health International, Durham, NC.; Karg C; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.; Randhawa A; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.; Hural J; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.; Gomez Lorenzo MM; Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.; Burns DN; Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.; Ledgerwood J; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.; Mascola JR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.; Cohen M; Department of Medicine, University of North Carolina, Chapel Hill, NC.; Corey L; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.; Mngadi K; Aurum Institute, Johannesburg, South Africa; and.; Mgodi NM; University of Zimbabwe Clinical Trials Research Center, Harare, Zimbabwe.
Source
Publisher: Lippincott Williams & Wilkins, Inc Country of Publication: United States NLM ID: 100892005 Publication Model: Print Cited Medium: Internet ISSN: 1944-7884 (Electronic) Linking ISSN: 15254135 NLM ISO Abbreviation: J Acquir Immune Defic Syndr Subsets: MEDLINE
Subject
Language
English
Abstract
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.
Competing Interests: S.R.W. has received clinical trial funding from Janssen Vaccines. The other authors have no conflicts of interest to disclose.
(Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
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.
Competing Interests: S.R.W. has received clinical trial funding from Janssen Vaccines. The other authors have no conflicts of interest to disclose.
(Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)