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Chronic, Acute, and Reactivated HIV Infection in Humanized Immunodeficient Mouse Models
Published on: December 3, 2019
Susceptibility to 3BNC117 and 10-1074 in ART suppressed chronically infected persons
Pablo Tebas1, Kenn Lynn1, Livio Azzoni2
1University of Pennsylvania.
Objective:
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.
Design:
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.
Method:
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 microg/ml and 1.5 microg/ml for 3BNC117 and 10-1074, respectively.
Results:
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.
Conclusions:
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.
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