Pharmacogenetics in HIV Therapy
Sonia Rodríguez-Novoa 1, Pablo Barreiro 2, Inmaculada Jiménez-Nácher 1, Ana Rendón 1, Vicente Soriano 3
1 NULL; 2 Department of Infectious Diseases, Hospital Carlos III-La Paz University Hospital. Madrid, Spain; 3 UNIR Health Sciences School and Medical Center, Universidad Internacional de La Rioja, Madrid, Spain
*Correspondence: Ana Rendón, Email not available
Abstract
Administration of standard doses of most antiretroviral drugs results in significant variations inplasma drug concentrations among different individuals, as well as different rates of drug-associatedtoxicity. The reasons for the large interindividual variability in drug levels are multifactorial, andinvolve differences in gender metabolism, concomitant medications, drug compliance, underlyingdiseases, and genetic factors. Pharmacogenetics is the discipline that analyses the genetic basisfor the interindividual variation in the body disposition of drugs. One of the main goals is to givegrounds to individualized therapy.The majority of pharmacogenetic traits so far have involved drug metabolism. An example of this isthe inherited variation in the pharmacokinetics and pharmacodynamics of drugs such as hydralazineor isoniazid. This variation is due to polymorphisms in the N-acetyltransferase-2 (NAT2) gene, whichmay split the population into three categories: slow, intermediate, and fast metabolizers.Pharmacogenetic studies conducted so far with antiretrovirals have focused on metabolizing enzymesand transporter proteins in the cell membrane. Herein, we review the genetic polymorphismsknown to be associated with altered pharmacokinetics of antiretrovirals, which may influence theefficacy and toxicity of these drugs.
