Abstract Body

Reduced susceptibility may limit the utility of broadly neutralizing anti-HIV monoclonal antibodies (bnAbs) in the prevention and treatment of HIV. At the present time, the PhenoSense mAb Assay is the only CLIA/CAP compliant screening test available to assess bnAb susceptibility in ARV suppressed individuals.

We used the PhenoSense mAb Assay, a phenotypic assay to assess the susceptibility of luciferase-reporter pseudovirions bearing populations of PBMC-derived HIV-1 envelope proteins to evaluate susceptibility to 3BNC117 and 10-1074 bnAbs. The results are expressed as the concentration of bnAb required to inhibit virus infectivity by 50%, 80%, 90% and 95% (IC50, IC80, IC90 and IC95, respectively), as well as the maximum percent inhibition (MPI). JRFL is used as an internal control. We evaluated mAb susceptibility for sensitivity to 3BNC117 and 101074 arbitrarily defined for the BEAT2 study (based in limited previous studies) as an IC90 < 2.0 µg/mL for 3BNC117 and <1.5 µg/mL for 10-1074.

We enrolled 61 ART suppressed (<20 copies/?L) participants with CD4+ T-cell counts ?450 cells/?L and nadir >200 c/mm3; 9 female, 1 transgender, 8 Caucasian (3/8 Hispanic), 53 African American. Nine of 61 (15%) did not amplify initially. Five of those were repeated and 2 amplified for a total of 54. Forty-one of 54 (76%) participants harbored virus exhibiting susceptibility to 3BNC117 and 37 of 54 (69%) exhibiting susceptibility to 10-1074. Thirty of 54 (56%, 95% CI 41-69)) were susceptible to both bnAbs and met study eligibility criteria. Although the IC90 for 10-1074 was lower than 3BNC117, the percentage of isolates with IC90 above the 10-1074 susceptibility cutoff was greater than the 3BNC117 cutoff (Figure). There was no correlation between bnAbs susceptibility (r=0.10 p=0.45 (Spearman)). Age, gender and race were no associated with susceptibility.

Approximately 50% of the chronically infected, virologically suppressed individuals harbored virus with reduced susceptibility to one or both of these mAbs. This is a potential limitation of combining only two bnAbs as PREP or treatment, as a significant proportion of the circulating virus variants are likely to exhibit reduced susceptibility to at least one mAb. Further studies defining and validating the clinical correlates of bnAb susceptibility thresholds for therapeutic maintenance protocols and curative treatment strategies are urgently needed.