A Novel Method to Optimize Drug Delivery for Parenteral Products Involving New Therapies and Unmet Needs.

Healthcare trends continue to move from hospital to home and many targeted therapies and precision medicines are now being designed to be self-administered by patients or delivered in a home setting. In the case of long acting injectables and bio-therapeutics, the importance of optimal drug/biologic-device combination in terms of user needs becomes critical for successful clinical outcomes. The risk especially increases for novel therapies due to unknowns and uncertainties surrounding new formulation flow behavior, delivery methods, new injection sites and therapeutic optimization.

The HIV-1 protease substitution K55R: a protease-inhibitor-associated substitution involved in restoring viral replication.

Objectives: The identification and in vitro characterization of novel protease mutations strongly associated with known protease resistance mutations.

Methods: The association between pairs of protease amino acid substitutions was identified using a database of protease sequences derived from protease inhibitor-experienced patients (n = 803). In vitro characterization included drug susceptibility and viral replication studies performed on recombinant viruses harbouring site-directed mutations.