Pharmacogenetics of the metabolic disturbances and atherosclerosis associated with antiretroviral therapy in HIV-infected patients.
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.
Veloso
Sergi
S
Hospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili, Tarragona, Spain.
Peraire
Joaquim
J
Viladés
Consuelo
C
López-Dupla
Miguel
M
Escoté
Xavier
X
Olona
Montserrat
M
Garcia-Pardo
Graciano
G
Gómez-Bertomeu
Frederic
F
Soriano
Antoni
A
Sirvent
Joan-Josep
JJ
Vidal
Francesc
F
D000818:Animals; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods; D050197:Atherosclerosis / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015658:HIV Infections / Q000188:drug therapy; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D006801:Humans; D007333:Insulin Resistance; D008659:Metabolic Diseases / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D010597:Pharmacogenetics
D019380:Anti-HIV Agents