Pharmacogenetics of Adverse Effects Due To Antiretroviral Drugs

The availability of highly active antiretroviral therapy has markedly improved the survival rate and qualityof life in patients infected with HIV. At present, however, there is still no cure for HIV and those undergoingtreatment have to do so for life. The use of antiretroviral drugs has been associated with several toxicitiesthat limit their success. Some acute and chronic toxicities associated with these drugs includehypersensitivity reactions, neurotoxicity, nephropathy, liver damage, and the appearance of body fatredistribution syndrome and the different metabolic alterations that accompany it. Some of these toxicitiesare family- or even drug-specific. Since not all patients that take a particular antiretroviral medicationdevelop the adverse effect that has been attributed to that drug, it has therefore been postulated thatthere must be a genetically conditioned individual predisposition to developing the adverse effect.Pharmacogenetics is the science that studies interindividual variations in the response to and toxicityof pharmaceuticals due to variations in the genetic composition of individuals – in other words, howa person’s genetic make-up influences the favorable or adverse effects of a certain treatment. Sufficientadvances have been made in this discipline to allow this fertile field of research to move out of thebasic science laboratory and into clinical applications. The present article reviews the investigationsthat have been published regarding the association between genetic determinants of persons infectedwith HIV and clinical toxicity resulting from different antiretroviral drugs. Special emphasis is devotedto the studies that have resulted in clinical applications such as that of the pre-screening of HLA B*5701for avoiding abacavir-related hypersensitivity syndrome.