PRO140 is a humanized CCR5 mAb with potent antiviral activity of ≥1.65 log10 mean viral load (VL) reduction as a weekly subcutaneous injection (SC) in patients infected with only CCR5-tropic HIV-1. This open-label, single-arm phase 2b extension study evaluated long-term suppression of HIV-1 replication by PRO140 SC monotherapy (MT) following initial antiretroviral therapy (ART).
42 adult patients on ART and infected with only CCR5-tropic HIV-1 (11-cohort 1, 28-cohort 2, 3-cohort 3) with VL <40 c/mL (LabCorp) were switched to weekly PRO140 350 mg SC MT. Following maintenance of viral suppression for 13 weeks, 17 subjects in cohort 2 and 3 were trained to self-administer PRO140 SC and offered continuation of MT in an ongoing extension study.
16 eligible subjects (87.5% male, 19% non-white) with median age of 54.9 years (26-68) and median CD4 T-cell count of 593 cells/mm3 (365-1059) were enrolled. One patient discontinued at week 47 (with VL <40 c/mL) due to relocation and 5 subjects experienced virologic failure (VF) (2 consecutive VL ≥400 c/mL). The mean time to VF was 329 days (106-691). 10 subjects are currently on PRO140 SC MT of which 9 subjects have completed nearly 2 years of treatment (93–106 weeks). 7 patients reported single-copy HIV-1 RNA values of <1 c/mL; 3 subjects reported values of 4, 10, and 19 c/mL (bioMONTR Labs). Prior to study entry, all subjects were infected with only CCR5-tropic HIV-1 by Trofile® DNA Co-receptor Tropism Assay (LabCorp). Co-receptor tropism was reassessed at VF by Trofile® RNA Assay and no change was reported. PhenoSense® Entry (LabCorp) results for PRO140, maraviroc, and AMD3100 showed no significant change in post-treatment IC50, IC90 and fold change values compared with baseline results in VF and non-VF group of subjects. Anti-PRO140 antibodies were not detected in any subject. PRO140 was generally well tolerated with no drug-related major adverse events or treatment discontinuation reported.
In this phase 2b extension study, patients infected with only CCR5-tropic HIV-1 and virologically suppressed on ART were switched to weekly self-administered PRO140 350 mg SC MT. For nearly 2 years, PRO140 SC MT provided maximal virologic suppression, was well tolerated, and enabled the avoidance of potential toxicity of ART while preserving drug options. These results support further development of PRO140 SC as a simple, long-acting, single-agent maintenance therapy after initial ART in selected HIV-1 infected patients.