Susceptibility to 3BNC117 and 10-1074 in ART suppressed chronically infected persons

• Published in: AIDS (London) Vol. 37; no. 8; pp. 1203 - 1207
• Main Authors: Tebas, Pablo, Lynn, Kenn, Azzoni, Livio, Cocchella, Giorgio, Papasavvas, Emmanouil, Fair, Matthew, Karanam, Brijesh, Sharma, Paridhima, Reeves, Jacqueline D., Petropoulos, Christos J., Lalley-Chareczko, Linden, Kostman, Jay R., Short, Willian, Mounzer, Karam, Montaner, Luis J.
• Format: Journal Article
• Language: English
• Published: England Lippincott Williams & Wilkins 01-07-2023
• Subjects: Antibodies, Monoclonal - therapeutic use; Antibodies, Neutralizing; Broadly Neutralizing Antibodies; HIV Antibodies; HIV Infections; HIV-1; Humans; Luciferases
• ISSN: 0269-9370; 1473-5571; 1473-5571
• DOI: 10.1097/QAD.0000000000003575

The aim of this study was to assess the susceptibility of HIV to two HIV monoclonal antibodies (bnAbs), 3BNC117 and 10-1074, in individuals with chronically antiretroviral therapy (ART) suppressed HIV infection.
The susceptibility of bnAbs was determined using the PhenoSense mAb Assay, which is a cell-based infectivity assay designed to assess the susceptibility of luciferase-reporter pseudovirions. This assay is the only Clinical Laboratory Improvement Ammendment (CLIA)/College of American Pathologist (CAP) compliant screening test specifically developed for evaluating bnAb susceptibility in people with HIV infection.
The susceptibility of luciferase-reporter pseudovirions, derived from HIV-1 envelope proteins obtained from peripheral bloodmononuclear cells of 61 ART-suppressed individuals, to 3BNC117 and 10-1074 bnAbs was assessed using the PhenoSense mAb assay. Susceptibility was defined as an IC 90 of <2.0 μg/ml and 1.5 μg/ml for 3BNC117 and 10-1074, respectively.
About half of the individuals who were chronically infected and virologically suppressed were found to harbor virus with reduced susceptibility to one or both of the tested bnAbs.
The reduced combined susceptibility of 3BNC117 and 10-1074 highlights a potential limitation of using only two bnAbs for pre-exposure prophylaxis or treatment. Further studies are needed to define and validate the clinical correlates of bnAb susceptibility.