Pharmacogenetics of the Metabolic Disturbances and Atherosclerosis Associated with Antiretroviral Therapy in HIV-Infected Patients

Sergi      Veloso; Joaquim      Peraire; Consuelo      Vilades; Miguel      Lopez-Dupla; Xavier      Escote; Montserrat      Olona; Graciano      Garcia-Pardo; Frederic      Gomez-Bertomeu; Antoni      Soriano; Joan-Josep      Sirvent; Francesc      Vidal

doi:10.2174/138161210793563518

Abstract

The availability of highly active antiretroviral therapy has markedly improved the survival rate and quality of life in patients infected with HIV. At present, however, there is still no cure for HIV and those undergoing treatment have to do so for life. The use of antiretroviral drugs has been associated with several toxicities that limit their success. Some acute and chronic toxicities associated with these drugs include hypersensitivity reactions, neurotoxicity, nephropathy, liver damage, the appearance of body fat redistribution syndrome and the different metabolic alterations that accompany it. Some of these toxicities are family- or even drug-specific. Since not all patients that take a particular antiretroviral medication develop the adverse effect that has been attributed to that drug, it has therefore been postulated that there 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 toxicity of drugs due to variations in the genetic composition of individuals. Sufficient advances have been made in this discipline to allow this fertile field of research to move out of the basic science laboratory and into clinical applications. The present article reviews the investigations that have been published regarding the association between the genetic determinants of persons infected with HIV and the metabolic toxicity and chronic vascular consequences resulting from antiretroviral drugs. The influence of host genetic variants on dyslipidemia, hyperglycemia and insulin resistance, lipodystrophy and atherosclerosis are presented and discussed.

Keywords: HIV, HAART, adverse effects, pharmacogenetics, dyslipidemia, insulin resistance, lipodystrophy, atherosclerosis