Genetics in Efavirenz Metabolism, the GEM study

Summary Genetics in Efavirenz Metabolism, the GEM study:

In the standard treatment of the HIV infected patients of the Medical Centre
Haaglanden, location Westeinde and the HAGA teaching hospital, location Leyweg,
therapeutic drug monitoring for HIV medication, like efavirenz, is standard.
During therapeutic drug monitoring, some patients drew our attention. These
patient showed high drug levels whilst using normal efavirenz dosage. This
observation has led to the development of a study to find an explanation for
this phenomenon.

Efavirenz is a Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI), that is
commonly used as first line treatment in Highly Active Anti Retroviral Therapy
(HAART). This to prevent progression of the HIV infection. Efavirenz has a
defined therapeutical range of 1 * 4 mg/l. A drug level over 4mg/l is
associated with side effects. A drug level under 1mg/l is associated with a
higher change of therapeutic failure.

Efavirenz is metabolised in the liver, by CYP2B6 enzyme. In CYP2B6 various
Single Nucleotide Polymorphisms (SNP) are described, that possibly affect the
capacity of the CYP2B6 enzyme to metabolise efavirenz. Variations in CYP2B6
could be an explanation as to why some patients have abnormal drug levels of
efavirenz.

These findings have led to the development of the following research questions:
Are variations in genetic markers, e.g. CYP2B6 (subtype *6, *7 and *18), for
the metabolism of efavirenz, an explanation for the abnormal pharmacokinetics
in the HIV population of the participating hospitals?

Is it possible to connect the variations in genetic markers to
specific population characteristics?

The study is a pilot study, designed an a multi-centre explorative case-control
study.

To find an explanation for the abnormal blood levels of efavirenz. With the
main research question: Are variations in genetic markers, e.g. CYP2B6 (subtype
*6, *7 and *18), for the metabolism of efavirenz, an explanation for the
abnormal pharmacokinetics in the HIV population of the participating hospitals?

Pilot study, designed as a multi-centre explorativ case-control study

An extra bloodsample (4ml) is taken from the participant. This bloodsample will
be taken on the same moment that the routine bloodsample for therapy control is
collected. Because these bloodsamples are beeing collected at the same moment,
there will be no additional risk/burden for the participant.