Kurzfassung

The non-nucleoside reverse transcriptase inhibitor nevirapine is widely used to prevent mother-to-child transmission of HIV-1. Unfortunately, nevirapine exhibits a low genetic barrier, with HIV-1 resistance after single-dose of nevirapine found in 25-48% of treated women. The resistance is related to the long elimination half-life of nevirapine. In consequence, nevirapine may become ineffective in subsequent nevirapine treatments of the same patients, including following pregnancies....The non-nucleoside reverse transcriptase inhibitor nevirapine is widely used to prevent mother-to-child transmission of HIV-1. Unfortunately, nevirapine exhibits a low genetic barrier, with HIV-1 resistance after single-dose of nevirapine found in 25-48% of treated women. The resistance is related to the long elimination half-life of nevirapine. In consequence, nevirapine may become ineffective in subsequent nevirapine treatments of the same patients, including following pregnancies. Furthermore, nevirapine-resistant HIV strains may spread in the population, reducing the efficiency of this important drug. A remedy to this problem could be provided by reducing the half-life of nevirapine through induction of its enzymatic disposition via CYP2B6 and CYP3A4/5. This hypothesis is currently being tested in two clinical studies in Africa. The purpose of this subproject is to assess the impact of the individually variable level of CYP2B6 and CYP3A4/5 on the response to induction. To this end, the expression level of CYP2B6 and CYP3A4/5 will be assessed by genotyping and phenotyping methods. This should enable stratification of study participants according to the individual expression of these enzymes. It is hoped that these analyses will facilitate the detection of the induction effect on nevirapine disposition.


L'Homme R, F., T. Dijkema, et al. (2006). "Brief report: enzyme inducers reduce elimination half-life after a single dose of nevirapine in healthy women." J Acquir Immune Defic
Syndr 43(2): 193-6.

Owen, A., M. Pirmohamed, et al. (2006). "Pharmacogenetics of HIV therapy."
Pharmacogenet Genomics 16(10): 693-703.
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