Development of screening assays for use of broadly neutralizing antibodies in people with HIV

Abstract

Purpose of review Treatment with combinations of complementary broadly neutralizing antibodies (bnAbs) has increased the proportion of participants for whom bnAbs can maintain virus suppression upon cessation of antiretroviral therapy (ART). There remains, however, a population of trial participants who experience virus rebound despite high plasma concentrations of bnAbs. Thus, baseline resistance remains a critical barrier to the efficacy of bnAbs for use in the treatment and cure of HIV, and the development of a screening assay to guide bnAb selection is a high priority. Recent findings There are two conceptual approaches to assess the putative rebound-competent HIV-1 reservoir for bnAb sensitivity: to assess neutralization sensitivity of reactivated virus in outgrowth assays and sequence-based approaches that include a selection for intact genomes and assessment of known resistance mutations within the env gene. Currently, the only phenotypic assay for bnAb screening that is clinical laboratory improvement amendments certified (CLIA certified) and available for clinical trial use is Monogram Biosciences’ PhenoSense HIV Neutralizing Antibody Assay. Summary Several new approaches for screening are currently under development and future screening methods must address three issues. First, complete sampling of the reservoir may be impossible, and determination of the relevance of partial sampling is needed. Second, multiple lines of evidence indicate that in vitro neutralization measures are at least one correlate of in vivo bnAb activity that should be included in screening, but more research is needed on how to use in vitro neutralization assays and other measures of antibody functions and measures of other antibody features. Third, the feasibility of screening assays must be a priority. A feasible, predictive bnAb screening assay will remain relevant until a time when bnAb combinations are substantially more broad and potent.