O121 Drug interactions that really matter

Recognising and managing drug-drug interactions (DDI) has become a necessary part of antiretroviral therapy. One study has identified significant DDIs in around one in five patients receiving ARVs (antiretroviral therapy) in the USA, ~20% of which could have resulted in decreased exposure to HIV drugs. Despite this, awareness of potential DDIs is all too often poor. Although screening may be comprehensively undertaken, the characterisation of potential DDIs during the drug development process is at best incomplete, and unanticipated DDIs continue to surprise. Recent examples are: rosuvastatin with LPV/r, and co-administration of boosted PIs to healthy volunteers receiving rifampicin. Recent advances in our understanding of pharmacological mechanisms have highlighted the importance of drug transporters (including influx transporters such as SLCO1B1) and key regulatory nuclear transcription factors such as PXR and CAR in mediating drug interactions. In addition, pharmacogenetic variability may impact on inter-individual differences in the magnitude of DDIs. This talk will provide an overview of new developments in our understanding of the molecular mechanisms of DDIs, identify important DDIs affecting 'newer' ARVs and discuss the public health aspects of DDIs in both the developed, and developing world.