Pharmacogénétique et antirétroviraux : le cas du Darunavir et du Raltegravir

The human immunodeficiency virus (HIV) affects nearly 37 million people worldwide. Combination antiretroviral therapy (cART) has radically changed the natural evolution of the infection allowing prolonged survival and preventing HIV transmission. However, eradication of HIV cannot be achieved with current cART. Thereby, lifelong, chronic therapy without treatment interruption is the standard of care exposing patients to a risk of toxicity. In addition, the inter-individual variability in the response to ARV is well known. The aim of this work was to assess the impact of genetic polymorphisms affecting metabolizing enzymes (CYP3A, UGT1A1) and transport proteins (ABCB1 and OTAP) on two ARV drugs: Darunavir (DRV) and Raltegravir (RAL). In relation to DRV, a major interaction between DRV and Etravirine in patients expressing CYP3A5 (which is very common in Africans, whereas it is rare in Caucasians) has been demonstrated for the very first time. CYP3A5 expressors might be more at risk of infra-therapeutic DRV plasma concentrations when ETR is included in their therapeutic regimen. Concerning RAL, a significant impact of the UGT1A1*28 polymorphism has been demonstrated on RAL exposure. Pharmacogenetics can therefore contribute to the improvement of clinical response in the field of antiretroviral therapy.(MED - Sciences médicales) -- UCL, 201