Risks and synergies from drug interactions.

AIM

To review what is known from in vitro and in vivo studies about the interactions, both potentially beneficial and potentially harmful, of antiretroviral agents with each other and with other classes of drugs.

INTERACTIONS WITH NUCLEOSIDE ANALOGUES

Some interactions between nucleoside HIV reverse transcriptase inhibitors and between nucleoside analogues and HIV protease inhibitors result in greater antiretroviral activity (e.g. zalcitabine with saquinavir). Others may increase the risks of toxicity and there are a number of combinations of nucleoside agents with other drugs that should be used with caution or avoided completely.

INTERACTIONS WITH PROTEASE INHIBITORS

These drugs are metabolized by cytochrome P450 CYP3A4 in the liver; because they have the potential to inhibit this enzyme they may interact with many other drugs that are metabolized by this pathway. Ritonavir also inhibits other cytochrome P450 enzymes and so interacts with numerous drugs from a range of classes. Potentially beneficial interactions between protease inhibitors include the increase in saquinavir levels brought about by ritonavir.

CONCLUSIONS

Knowledge of additive and synergistic interactions between antiretroviral agents should facilitate development of therapeutic regimens with prolonged antiretroviral activity. Thorough investigation of possibly harmful interactions with co-administered drugs and education of clinicians and patients about the risks of these interactions is required.