In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 18, No. 3 ( 2022-3-31), p. e1010396-
Abstract:
The CCR5-specific antibody Leronlimab is being investigated as a novel immunotherapy that can suppress HIV replication with minimal side effects. Here we studied the virological and immunological consequences of Leronlimab in chronically CCR5-tropic HIV-1 infected humans (n = 5) on suppressive antiretroviral therapy (ART) and in ART-naïve acutely CCR5-tropic SHIV infected rhesus macaques (n = 4). All five human participants transitioned from daily combination ART to self-administered weekly subcutaneous (SC) injections of 350 mg or 700 mg Leronlimab and to date all participants have sustained virologic suppression for over seven years. In all participants, Leronlimab fully occupied CCR5 receptors on peripheral blood CD4+ T cells and monocytes. In ART-naïve rhesus macaques acutely infected with CCR5-tropic SHIV, weekly SC injections of 50 mg/kg Leronlimab fully suppressed plasma viremia in half of the macaques. CCR5 receptor occupancy by Leronlimab occurred concomitant with rebound of CD4+ CCR5+ T-cells in peripheral blood, and full CCR5 receptor occupancy was found in multiple anatomical compartments. Our results demonstrate that weekly, self-administered Leronlimab was safe, well-tolerated, and efficacious for long-term virologic suppression and should be included in the arsenal of safe, easily administered, longer-acting antiretroviral treatments for people living with HIV-1. Trial Registration: ClinicalTrials.gov Identifiers: NCT02175680 and NCT02355184 .
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1010396
DOI:
10.1371/journal.ppat.1010396.g001
DOI:
10.1371/journal.ppat.1010396.g002
DOI:
10.1371/journal.ppat.1010396.g003
DOI:
10.1371/journal.ppat.1010396.g004
DOI:
10.1371/journal.ppat.1010396.t001
DOI:
10.1371/journal.ppat.1010396.s001
DOI:
10.1371/journal.ppat.1010396.s002
DOI:
10.1371/journal.ppat.1010396.s003
DOI:
10.1371/journal.ppat.1010396.s004
DOI:
10.1371/journal.ppat.1010396.s005
DOI:
10.1371/journal.ppat.1010396.s006
DOI:
10.1371/journal.ppat.1010396.s007
DOI:
10.1371/journal.ppat.1010396.s008
DOI:
10.1371/journal.ppat.1010396.s009
DOI:
10.1371/journal.ppat.1010396.s010
DOI:
10.1371/journal.ppat.1010396.s011
DOI:
10.1371/journal.ppat.1010396.s012
DOI:
10.1371/journal.ppat.1010396.s013
DOI:
10.1371/journal.ppat.1010396.s014
DOI:
10.1371/journal.ppat.1010396.s015
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2205412-1