Background:
VRC07-523LS is a broadly neutralizing anti-HIV-1 envelope monoclonal antibody under investigation in combination with LA-cabotegravir for maintenance of HIV-1 suppression in the AIDS Clinical Trials Group (ACTG) A5357 study. Eligibility for A5357 required susceptibility to VRC07-523LS, defined as half-maximal inhibitory concentration (IC50) ≤ 0.25 μg/mL and a maximum percent inhibition (MPI) > 98% on the Monogram PhenoSense mAb Assay (Labcorp-Monogram Biosciences) using PBMCs collected at screening. The predictors and correlates of VRC07-523LS susceptibility have not been established; thus, we conducted this exploratory analysis to evaluate the range of PhenoSense mAb assay results and correlations with demographic and clinical variables.
Methods:
All participants screened for A5357 who had at least one PhenoSense mAb assay result were included in the analysis. Correlations between VRC07-523LS and the covariates were explored using Chi-Square tests (sex, race/ethnicity), Wilcoxon rank-sum rests (age, nadir CD4, and years since HIV diagnosis), and logistic regression. All analyses were exploratory with no adjustments for multiple testing.
Results:
We included 137 participants: 21% female, 1% transgender female, median age 52 years, 43% White, 38% Black, 15% Hispanic. Median nadir CD4 count was 305 cells/mm3 with a median of 15 years post HIV diagnosis. Based on the first Phenosense assay, 67% were reported as susceptible to VRC07-523LS and 14% as not susceptible; 19% were non-reportable. There were no significant differences in demographic characteristics between those with reported and non-reportable assay results. Nine of 26 participants with non-reportable results were rescreened using new PBMC aliquots, of which 4/9 (44%) were successfully assayed, all reported as VRC07 susceptible. Neutralization measurements showed correlation between IC50, IC80 and IC95 (r values 0.88-0.99). There was moderate negative correlation between years since HIV diagnosis and IC50 values (r=-0.20, p=0.034). We found no associations between the neutralization measures and the other variables considered.
Conclusions:
A5357 has conducted the highest number of baseline susceptibility assays for VRC07-523LS clinical trials to date. Approximately 70% of participants screened and tested met protocol-specified definition of VRC07-523LS susceptibility. A trend towards higher IC50 values for individuals who were more recently diagnosed was observed, which requires further evaluation.
Bar Chart of Neutralization Measurements