A calculated risk: Evaluating HIV resistance to the broadly neutralising antibodies10-1074 and 3BNC117.

Abstract

Purpose of this review: Broadly neutralising antibodies (bNAbs) are a promising new therapy for the treatment of HIV infection. However, the effective use of bNAbs is impacted by the presence of preexisting virological resistance and the potential to develop new resistance during treatment. With several bNAb clinical trials underway, sensitive and scalable assays are needed to screen for resistance. This review summarises the data on resistance from published clinical trials using the bNAbs 10-1074 and 3BNC117 and evaluates current approaches for detecting bNAb sensitivity as well as their limitations.

Recent findings: Analyses of samples from clinical trials of 10-1074 and 3BNC117 reveal viral mutations that emerge on therapy which may result in bNAb resistance. These mutations are also found in some potential study participants prior to bNAb exposure. These clinical data are further informed by ex-vivo neutralisation assays which offer an alternative measure of resistance and allow more detailed interrogation of specific viral mutations. However, the limited amount of publicly available data and the need for better understanding of other viral features that may affect bNAb binding mean there is no widely accepted approach to measuring bNAb resistance.

Summary: Resistance to the bNAbs 10-1074 and 3BNC117 may significantly impact clinical outcome following their therapeutic administration. Predicting bNAb resistance may help to lower the risk of treatment failure and therefore a robust methodology to screen for bNAb sensitivity is needed.