PRO 140 IN VITRO ACTIVITY IN HTE SUBJECTS WITH A 4
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Posted On: 03/10/2020 8:59:44 PM
PRO 140 IN VITRO ACTIVITY IN HTE SUBJECTS WITH A 4-CLASS DRUG-RESISTANT HIV-1 VIRUS
Author(s):
Stefano Rusconi1, Francesco Saladini2, Silvia Barbaliscia3, Andrea Poli4, Laura Galli4, Roberta Gagliardini5, Lidia Gazzola6, Daniela Francisci7, Francesca Vichi8
1University of Milan, Milan, Italy,2University of Siena, Siena, Italy,3University of Rome Tor Vergata, Rome, Italy,4San Raffaele Vita-Salute University, Milan, Italy,5Lazzaro Spallanzani National Institute for Infectious Diseases, Rome, Italy,6Azienda Ospedaliera San Paolo, Milan, Italy,7University of Perugia, Perugia, Italy,8Santa Maria Annunziata Hospital, Florence, Italy,9University of Brescia, Brescia, Italy
Abstract Body:
PRO 140 is a novel humanized form of a mouse immunoglobulin G4 CCR5-directed monoclonal antibody with nanomolar potency in inhibiting HIV-1 cell entry through the CCR5 coreceptor. The aim of this study was to analyze HIV-1 tropism and in vitro susceptibility to PRO 140 according to MVC exposure in a cohort of heavily treatment-experienced (HTE) HIV-1-infected patients (pts) harboring a documented 4-class drug-resistance to NRTIs, NNRTIs, PIs, InSTIs, enrolled in the Italian PRESTIGIO Registry.
Plasma RNA (viremic pts) or PBMC DNA (non-viremic pts) was used for Sanger sequencing and Next Generation Sequencing (NGS, Illumina platform) of the gp120-V3 region followed by geno2pheno [coreceptor] interpretation. Viral tropism and susceptibility to PRO 140 were assessed through a home-made phenotypic assay based on pseudotyped viruses expressing patient derived Env protein and luciferase as reporter gene. Pts demographics and laboratory data are described as median (Q1-Q3), mean (±SD) or frequency (%).
Among 25 pts, 20 (80%) were male, median age 50 years (44-53), time since HIV-1 diagnosis 23 years (19-26), time on ART 20 years (16-23), 14 (56%) with a previous AIDS diagnosis, 17 (68%) with maraviroc (MVC) exposure, a median CD4+ count 207 cells/l (73-326) and a median viral load 4.58 log10 copies/mL (4.02-5.11), with 2 pts with HIV-RNA
In this group of HTE pts with MDR virus, all CCR5-tropic strains were fully susceptible to PRO 140 and they were not significantly impacted by MVC exposure. PRO 140 can thus play a key role in subjects with very limited therapeutic options and CCR5-tropic virus.
Session Number:
P-I03
Session Title:
DRUG RESISTANCE IN EXPERIENCED AND POTENTIAL FOR SUCCESSFUL TREATMENT
Presenting Author:
Arianna Gabrieli
Presenter Institution:
University of Milan
https://www.croiconference.org/sessions/pro-1...iv-1-virus
Author(s):
Stefano Rusconi1, Francesco Saladini2, Silvia Barbaliscia3, Andrea Poli4, Laura Galli4, Roberta Gagliardini5, Lidia Gazzola6, Daniela Francisci7, Francesca Vichi8
1University of Milan, Milan, Italy,2University of Siena, Siena, Italy,3University of Rome Tor Vergata, Rome, Italy,4San Raffaele Vita-Salute University, Milan, Italy,5Lazzaro Spallanzani National Institute for Infectious Diseases, Rome, Italy,6Azienda Ospedaliera San Paolo, Milan, Italy,7University of Perugia, Perugia, Italy,8Santa Maria Annunziata Hospital, Florence, Italy,9University of Brescia, Brescia, Italy
Abstract Body:
PRO 140 is a novel humanized form of a mouse immunoglobulin G4 CCR5-directed monoclonal antibody with nanomolar potency in inhibiting HIV-1 cell entry through the CCR5 coreceptor. The aim of this study was to analyze HIV-1 tropism and in vitro susceptibility to PRO 140 according to MVC exposure in a cohort of heavily treatment-experienced (HTE) HIV-1-infected patients (pts) harboring a documented 4-class drug-resistance to NRTIs, NNRTIs, PIs, InSTIs, enrolled in the Italian PRESTIGIO Registry.
Plasma RNA (viremic pts) or PBMC DNA (non-viremic pts) was used for Sanger sequencing and Next Generation Sequencing (NGS, Illumina platform) of the gp120-V3 region followed by geno2pheno [coreceptor] interpretation. Viral tropism and susceptibility to PRO 140 were assessed through a home-made phenotypic assay based on pseudotyped viruses expressing patient derived Env protein and luciferase as reporter gene. Pts demographics and laboratory data are described as median (Q1-Q3), mean (±SD) or frequency (%).
Among 25 pts, 20 (80%) were male, median age 50 years (44-53), time since HIV-1 diagnosis 23 years (19-26), time on ART 20 years (16-23), 14 (56%) with a previous AIDS diagnosis, 17 (68%) with maraviroc (MVC) exposure, a median CD4+ count 207 cells/l (73-326) and a median viral load 4.58 log10 copies/mL (4.02-5.11), with 2 pts with HIV-RNA
In this group of HTE pts with MDR virus, all CCR5-tropic strains were fully susceptible to PRO 140 and they were not significantly impacted by MVC exposure. PRO 140 can thus play a key role in subjects with very limited therapeutic options and CCR5-tropic virus.
Session Number:
P-I03
Session Title:
DRUG RESISTANCE IN EXPERIENCED AND POTENTIAL FOR SUCCESSFUL TREATMENT
Presenting Author:
Arianna Gabrieli
Presenter Institution:
University of Milan
https://www.croiconference.org/sessions/pro-1...iv-1-virus
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