A metabolite produced during breakdown of a popular anti-viral drug used to treat HIV may be contributing to cognitive impairment in HIV infected individuals. As much as half of HIV infected people will develop some type of neurocognitive impairment that create problems performing common daily activities. Researchers at Johns Hopkins have implicated the drug Efavirenz as a contributing factor.
Efavirenz is in a class of medications called non-nucleoside reverse transcriptase inhibitors (NNRTIs). Efavirenz is a potent HIV inhibitor and is one of the few drugs known to cross the blood-brain barrier targeting potential reservoirs of virus in the brain. It has long been thought that this ability to potentially target reservoirs of virus in the brain would help alleviate neurocognitive disorders.
In the study led by Haughey and described online in the Journal of Pharmacology and Experimental Therapeutics, published online
September 13th (click here for the full study) showed that the metabolite 8-hydroxyefavirenz is damaging to brain tissue, by as much as 10 times the intact drug. Fortunately, Namandje N. Bumpus, Ph.D one of the co authors found that a relatively simple modification to the drugs structure may be able to prevent the formation of 8-hydroxyefavirenz while maintaining its ability to repress HIV.
"Finding and stating a problem is one thing, but it's another to be able to say we have found this problem and here is an easy fix," says Norman J. Haughey, Ph.D., an associate professor of neurology at the Johns Hopkins University School of Medicine. "People with HIV infections can't stop taking anti-retroviral drugs. We know what happens then and it's not good," "But we need to be very careful about the types of anti-retrovirals we prescribe, and take a closer look at their long-term effects. Drug toxicities could be a major contributing factor to cognitive impairment in patients with HIV."
This revelation regarding Efavirenz should be a reminder of why research for new drugs needs to be a high priority while also maintaining a constant vigil on potential side effects from the drugs themselves. Until a successful vaccine is created, HAART drugs will need to be taken every day for as long as an infected individual is alive. Therefore, long term safety issues are likely to show up after approval since clinical trials are not always predictive of extreme long term use.