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

• Type of Material: Article
• Authors: Simbarashe Takuva, Fred Hutchinson Cancer Research Center, Seattle; Shelly T Karuna, Fred Hutchinson Cancer Research Center, Seattle; Michal Juraska, Fred Hutchinson Cancer Research Center, Seattle; Erika Rudnicki, Fred Hutchinson Cancer Research Center, Seattle; Srilatha Edupuganti, Emory University; Maija Anderson, Fred Hutchinson Cancer Research Center, Seattle; Robert de la Grecca, Fred Hutchinson Cancer Research Center, Seattle; Martin R Gaudinski, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Alice Sehurutshi, Botswana Harvard AIDS Institute, Gaborone; Catherine Orrell, University of Cape Town; Logashvari Naidoo, South African Medical Research Council; Javier Valencia, Asociacion Civil Impacta Salud y Educacion, Lima, Peru; Larissa M Villela, Fundação Oswaldo Cruz (INI-Fiocruz), Rio de Janeiro, Brazil; Stephen R Walsh, Brigham and Women’s Hospital, Boston, MA; Philip Andrew, Family Health International, Durham, NC; Carissa Karg, Fred Hutchinson Cancer Research Center, Seattle; April Randhawa, Fred Hutchinson Cancer Research Center, Seattle; John Hural, Fred Hutchinson Cancer Research Center, Seattle; Margarita M Gomez Lorenzo, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; David N Burns, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Julie Ledgerwood, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; John R Mascola, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Myron Cohen, University of North Carolina; Lawrence Corey, Aurum Institute, Johannesburg, South Africa; Kathy Mngadi, Aurum Institute, Johannesburg, South Africa; Nyaradzo M Mgodi, University of Zimbabwe
• Language: English
• Date: 2022-04-01
• Publisher: LIPPINCOTT WILLIAMS & WILKINS
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2021 Wolters Kluwer Health, Inc. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1097/QAI.0000000000002892
• Title of Journal or Parent Work: JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
• Volume: 89
• Issue: 4
• Start Page: 405
• End Page: 413
• Grant/Funding Information: AI068614, AI068635, AI068618, AI068619, AI069412
• Keywords: broadly neutralizing antibodies; infusion-related reactions; HIV; SAFETY; Infectious Diseases; MANAGEMENT; Science & Technology; MONOCLONAL-ANTIBODY; DIAGNOSIS; Immunology; VRC01; Life Sciences & Biomedicine; hypersensitivity; AMP study

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.