Inter-individual variability in pharmacokinetics and response to protease inhibitor-based antiretroviral therapy

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Treatment for HIV clearly improves survival. However, some patients fail therapy either because of toxicity or because the virus mutates, allowing it to multiply even in the presence of the drug. Both of these factors are strongly influenced by the amount of drug that enters a patient?s bloodstream. For example, too much drug and the patient will experience some types of toxicity and too little drug and the virus is able to try out different mutations, eventually finding those which allow it to survive. Our knowledge of the factors that influence drug concentrations in the blood is rapidly developing. Our recent work has shown that SLCO transporters, which are molecular pumps that transfer anti-HIV drugs into gut and liver cells can influence the absorption and clearance of some drugs from the body. These transporters are encoded by the human genome and there are differences in these genes meaning that in some individuals they have different activity than in others. Therefore, the reason for this research is to assess whether differences in SLCO transporter genes are able to explain some of the differences in drug concentrations and susceptibility to toxicity and failure of anti-HIV drugs. Ultimately, if this project is successful it will aid the development of tests that help HIV doctors to give the right drug, at the right dose to the right patient.