Effect of genetic variation on HIV drug levels

By investigating the impact of genetic variation on ARVs, investigators would like to be able to prescribe the exact dose of a drug for an individual patient. In this way, resistance and treatment failure from too low a dose or drug toxicity from too high a dose can be avoided.

A number of factors are responsible for determining the levels of a drug, including gender, other medications or foods the patient is taking, drug adherence, underlying diseases, and genetic factors. Pharmacogenetic studies of drug levels have mainly concentrated on genes that encode enzymes that transport drugs into and out of the body, such as the multidrug resistance proteins (including poly-glycoprotein), and enzymes that metabolise drugs.

While a large number of associations have been identified, none has proved to be robust enough to be introduced as a test in HIV treatment. In addition, these polymorphisms have not always been associated with the expected differences in response to antiretroviral therapy, in terms of virological suppression, risks of treatment failure, and immune reconstitution. This suggests that the links between genetics, drug levels, and treatment outcomes are complex and will require more research before they are fully understood.