ABSTRACT
The discovery of maraviroc (MVC; Selzentry®; ViiV Healthcare), a CCR5 antagonist administered for the treatment of HIV-1 infection, necessitated the development of a diagnostic assay to identify patients most likely to respond to treatment with MVC because it is only active against CCR5-tropic strains of HIV. This section discusses the development and optimization of a novel phenotypic tropism assay and its use during the MVC clinical development program. It demonstrates how the results of clinical studies confirmed the utility of the assay in the clinical setting and how optimization of assay performance over time impacted the clinical development program. The development and evaluation of genotypic tropism tests that have the potential to allow for local use and more rapid turnaround times are also discussed, as are the more recent development of DNA-based tropism assays to facilitate the use of CCR5 antagonists in virologically suppressed patients, thereby increasing the size of the patient population that could benefit from CCR5-antagonist treatment.
