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Drug metabolism

Most of the currently available ARVs are substrates of polymorphic drug metabolising enzymes, transporters and receptors. For example, efavirenz and nevirapine, used as part of the first line antiretroviral therapy (ART) regimens, are principally metabolised by CYP2B6 and to a lesser extent by CYP1A2, CYP2A6, CYP3A4 and CYP3A5. Variation in the gene (ABCB1) coding for the multidrug resistance protein, P-gp and the orphan receptors PXR and CAR forms a strong focus of the group. In addition to HIV/AIDS, most of these enzymes are also involved in the metabolism of drugs used for the treatment of other disorders including schizophrenia, cancer, diabetes and malaria. Our group is involved in examining whether interindividual differences in response to these drugs are due to polymorphisms in these genes.

Another area of active research is genetic characterisation of mitochondrial mutations for (a) their role in the response to stavudine containing ARV regimens and (b) contribution in defining Black African populations with respect to mtDNA haplogroups.