HIV Drug May Not be as Effective in Some African Americans

A protein found in nearly half of African Americans speeds removal of medication from the body.

A protein more prevalent in African Americans may prevent them from getting effective doses of the HIV drug maraviroc, according to the results of a study from the Johns Hopkins University School of Medicine.

Published online on August 12, 2014 in the journal Drug Metabolism and Disposition, the study examines whether people with maximum levels of the protein CYP3A5 retain less of the same dosage of maraviroc in their bodies compared with people who lack the protein. When initial dosing studies were completed before maraviroc was licensed in 2007, the trial included mostly European Americans, who generally lack CYP3A5.

"Because African-Americans are disproportionately affected by HIV infection, it is doubly important that we get the dosing right," said Namandje Bumpus, PhD, an assistant professor of pharmacology and molecular sciences at Johns Hopkins in a press release.

The CYP3A5 protein, which is found in liver and intestinal cells, adds an oxygen molecule to drugs that make it more water soluble and causes the drug to enter the urine and leave the body. An estimated 80% to 90% of European Americans lack CYP3A5, while 45% of African Americans possess the protein.

With drugs like maraviroc, CYP3A5 plays a prominent role in removing the treatments from the body. As a result, the researchers hypothesized that the recommended dose of maraviroc may be insufficeint for African Americans, who possess 2 functional copies of the CYP3A5 gene.

For the study, the researchers examined 24 healthy volunteers by the number of functional copies of the CYP3A5 gene they have, from zero to 2. The subjects were given a single 300 milligram dose of maraviroc and then had their blood taken at 10 time intervals over a period of 32 hours.

The amount of maraviroc were similar for the groups with zero or 1 functioning copies of the CYP3A5 gene at each time point. Concentration of the drug were lower, however, in people with 2 functioning copies.

People with 2 functioning copies of the gene had a 41% lower concentration of the drug overall than the other groups. Additionally, those with 2 functioning copies of the gene had an average drug concentration just above the lowest level that is deemed to be effective against HIV.

Meanwhile, 4 of the 8 people with 2 functioning copies of the gene had individual average concentration that dropped below the lowest effective level.

"The trend we saw was that the more functional CYP3A5 a person had, the faster maraviroc was processed and left the body, so the lower its concentration in the bloodstream," Bumpus said. "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."