Efavirenz is an important drug for treating HIV infection, but it has negative effects that can significantly impact patients' quality of life over time. It causes neuropsychiatric disorders and neurocognitive impairment in roughly 50 percent of patients. The drug is associated with abnormal lipid levels in blood plasma, but the molecular mechanisms responsible for negative clinical observations are unknown.
A new study in ACS Pharmacology & Translational Science led by Nav Raj Phulara, a chemistry graduate student at the University of Maryland, Baltimore County (UMBC), used a novel combination approach to increase understanding of the relevant mechanisms. First, tissue imaging showed that Efavirenz alters lipid metabolism in mouse brains. Next, the researchers investigated all of the proteins present in the mouse brain sections and found that Efavirenz downregulates certain enzymes.
All of these changes could be responsible for the drug's negative neuropsychiatric effects. If proven so, new drugs could potentially be developed to block the negative activity of Efavirenz while allowing its positive effects to continue. Lipid abnormalities in the brain can lead to adverse effects like brain disorders and neurodegenerative diseases, and the brain is rich in lipids overall.
That formed the basis for investigating lipids in this study." Herana Kamal Seneviratne, Study Senior Author and Bioanalytical Chemist, University of Maryland Baltimore County The new combination approach cou.