Currently prescribed doses of maraviroc, an HIV medication, are ineffective for half of African Americans due to the overproduction of a protein that rapidly removes the drug from their bodies.
Currently prescribed doses of maraviroc, an HIV medication, are ineffective for half of African Americans due to the overproduction of a protein that rapidly removes the drug from their bodies, recent research claimed.
Found in liver and intestinal cells, Cytochrome P450 3A5 (CYP3A5) proteins add oxygen to drugs such as maraviroc, making the medication water-soluble and quickly expelled through urine.
Previous maraviroc dosing studies observed mostly European American participants, 80% to 90% of which lack functional CYP3A5 proteins, according to John Hopkins Medicine. For a staggering portion of African Americans, their CYP3A5 proteins were found to not only be functional, but they also had the maximum amount of them.
“Because African-Americans are disproportionately affected by HIV infection, it is doubly important that we get the dosing right,” Namandje Bumpus, PhD, of the Johns Hopkins University School of Medicine, said in a statement.
The study, published in Drug Metabolism and Disposition, recruited 24 healthy patients and designated them into “mutant” (0 carriers), “heterozygous” (1 carrier), and “homozygous” (2 carriers) categories. From there, the researchers administered an oral dose of 300 mg of maraviroc, followed by 10 blood tests over a 32-hour time period.
Compared to subjects with 2 poorly working CYP3A5 proteins, carriers of 2 functional CYP3A5s had a 41% overall decrease in their levels of maraviroc. Individuals who had 2 operational proteins were consistently found to have lower maraviroc blood concentration.
Furthermore, these carriers had an average concentration of the drug in their system that barely made it effective.
From their findings, the researchers determined that since 45% of African Americans are homozygous for the protein, they are disproportionately being underdosed
“What’s nice is that, if a larger study confirms that we are underdosing this group, a simple genetic test prior to dosing decisions could rectify the situation,” Bumpus commented.