Plenary Lecture: New Frontiers in HIV Protease Inhibitors

The present protease inhibitors, as monotherapies, have various limitations.

1. Low plasma drug trough levels: partly due to low absorption, may be made still worse by protein binding.
2. There is a period in the dosing schedule during which HIV can replicate and so may develop resistance.
3. Although the primary mutation positions may differ for the various protease inhibitors, there are secondary mutation sites which are common to several inhibitors. These do not make the strain totally resistant to another inhibitor, but it does enlarge the window of time when HIV replication is not prevented.

A way forward was illustrated with ABT-378. When co-administered with a small dose of ritonavir, the plasma levels of ABT-378 are both high and long lasting. Once or twice daily dosing should keep the drug levels well above those needed to prevent HIV replication throughout the whole day. Simpler drug schedules will help patients from giving the virus chances for replication and gaining resistance.