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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
Takuva, Simbarashe et al. | Date Issued: 2022
Author
Takuva, Simbarashe
Karuna, Shelly T.
Juraska, Michal
Rudnicki, Erika
Edupuganti, Srilatha
Anderson, Maija
La Grecca, Robert De
Gaudinski, Martin R.
Sehurutshi, Alice
Orrell, Catherine
Naidoo, Logashvari
Valencia, Javier
Villela, Larissa M.
Walsh, Stephen R.
Andrew, Philip
Karg, Carissa
Randhawa, April
Hural, John
Lorenzo, Margarita M. Gomez
Burns, David N.
Ledgerwood, Julie
Mascola, John R.
Cohen, Myron
Corey, Lawrence
Mngadi, Kathy
Mgodi, Nyaradzo M.
Affilliation
Fred Hutchinson Cancer Research Center. Vaccine and Infectious Disease Division. Seattle, WA, USA / University of the Witwatersrand. Faculty of Health Sciences. Perinatal HIV Research Unit. Johannesburg, South Africa / University of Pretoria. Faculty of Health Sciences. School of Health Systems and Public Health. Pretoria, South Africa.
Fred Hutchinson Cancer Research Center. Vaccine and Infectious Disease Division. Seattle, WA, USA.
Fred Hutchinson Cancer Research Center. Vaccine and Infectious Disease Division. Seattle, WA, USA.
Fred Hutchinson Cancer Research Center. Vaccine and Infectious Disease Division. Seattle, WA, USA.
Emory University. Department of Medicine. Division of Infectious Disease. Atlanta, GA, USA.
Fred Hutchinson Cancer Research Center. Vaccine and Infectious Disease Division. Seattle, WA, USA.
Fred Hutchinson Cancer Research Center. Vaccine and Infectious Disease Division. Seattle, WA, USA.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Vaccine Research Center. Bethesda, MD, USA.
Botswana Harvard AIDS Institute. Gaborone, Botswana, South Africa.
University of Cape Town. Institute of Infectious Disease and Molecular Medicine. Desmond Tutu HIV Center. Department of Medicine. Cape Town, South Africa.
South African Medical Research Council. Durban, South Africa.
Asociacion Civil Impacta Salud y Educacion. Lima, Peru.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Brigham and Women's Hospital. Division of Infectious Diseases. Boston, MA, USA.
Family Health International. Durham, NC, USA.
Fred Hutchinson Cancer Research Center. Vaccine and Infectious Disease Division. Seattle, WA, USA.
Fred Hutchinson Cancer Research Center. Vaccine and Infectious Disease Division. Seattle, WA, USA.
Fred Hutchinson Cancer Research Center. Vaccine and Infectious Disease Division. Seattle, WA, USA.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Division of AIDS. Bethesda, MD, USA.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Division of AIDS. Bethesda, MD, USA.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Vaccine Research Center. Bethesda, MD, USA.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Vaccine Research Center. Bethesda, MD, USA.
University of North Carolina. Department of Medicine. Chapel Hill, NC, USA.
Fred Hutchinson Cancer Research Center. Vaccine and Infectious Disease Division. Seattle, WA, USA.
Aurum Institute. Johannesburg, South Africa.
University of Zimbabwe Clinical Trials Research Center. Harare, Zimbabwe.
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.
Keywords
Infusion related reactions
Hypersensitivity
Broadly neutralizing antibodies
AMP study
VRC01
HIV
 
Publisher
Lippincott Williams & Wilkins
Citation
TAKUVA, Simbarashe et al. 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 of Acquired Immune Deficiency Syndromes, v. 89, n. 4, p. 1-17, Apr. 2022.
DOI
10.1097/QAI.0000000000002892
ISSN
1525-4135
Notes
HVTN 703/HPTN 081 and HVTN 704/HPTN 085 Study Teams.