The aim of Maseng’s project is to look at human genetic variation at the gene (Cytochrome P2B6) level as a possible host co-factor in selecting for non-nucleoside reverse transcriptase inhibitors (NNRTI) drug resistance mutations. This gene codes for enzymes that metabolise EFV and NVP in the liver. The status of CYP2B6 gene will be compared among subjects without resistance and in subjects carrying major and minor resistant mutations.
The NNRTIs are one of the first line anti-retroviral combinations used in resource-limited countries like Botswana. The use of anti-retrovirals, just like antibiotics, carries a risk of selecting for drug resistant HIV strains. Maseng aims to test if human genetic variation in drug metabolism is a contributing factor in the development of drug resistance. Some people are unable to tolerate drugs in their systems leading to drug toxicity and adverse effects. This eventually determines poor adherence to the intake of drugs thereby creating a window of selection to resistance. Moreover, other subjects metabolise the drugs so rapidly that the drugs don’t reach their inhibitory concentration. This also has a possibility of leading to selection of drug resistance. So, how does this help? Determination of genetic variation in the metabolism and disposition of these drugs will help in drug prescription as research has proven to be selectively useful in improving drug safety and efficacy and at the same time, could be a useful tool in reducing the risk of selection for drug resistance.