HIV Drug Efavirenz Causes Memory Decline

Victims of HIV highly rely on number of medication to suppress the virus. A few of them even take drugs for decades. Till date most of the researchers were blinded with the assumption that the disease causes damage to the brain, but the new Johns Hopkins research suggest that the drug efavirenz may play a key role in triggering memory declines.

Efavirenz is used with other medications to treat victims of HIV or AIDS. One of the few that crosses the blood-brain barrier can target potential reservoirs of virus in the brain. 

Doctors were under the assumption that it is possible to improve cognitive impairment associated with HIV by getting more drugs into the brain

Researchers say, "More caution is needed because there may be long-term effects of these drugs on the brain."

The study that was led by Haughey is being described online in the Journal of Pharmacology and Experimental Therapeutics. 

"People with HIV infections can't stop taking anti-retroviral drugs. We know what happens then and it's not good," says Norman J. Haughey, Ph.D., an associate professor of neurology at the Johns Hopkins University School of Medicine. "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."

For the study the researchers obtained samples of blood and cerebrospinal fluid from HIV infected subjects who had been enrolled in the NorthEastern AIDS Dementais study. It was reported that these subjects were taking efavirenz. They then noticed the levels of the drug and its various metabolites, which are substances created when efavirenz is broken down by the liver. 

The next step involved conducting experiments on neurons cultured in the lab. The investigators observed the effects of 8-hydroxyefavirenz and other metabolites.  They noticed major structural changes when using low levels of 8-hydroxyefavirenz, including the loss of the important spines of the cells.

Namandje N. Bumpus, Ph.D., one of the study's other authors, has found a way to modify the drug to prevent it from metabolizing into 8-hydroxyefavirenz while maintaining its effectiveness as a tool to suppress the HIV virus.

Haughey and his colleagues said, "The 8-hydroxyefavirenz is 10 times more toxic to brain cells than the drug itself and, even in low concentrations, causes damage to the dendritic spines of neurons."

"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," Haughey says.

Haughey says, "Studies like his serve as a reminder that while people infected with HIV are living longer than they were 20 years ago, there are significant problems associated with the drugs used to treat the infection."

"Some people do seem to have this attitude that HIV is no longer a death sentence," he says. "But even with anti-retroviral treatments, people infected with HIV have shortened life spans and the chance of cognitive decline is high. It's nothing you should treat lightly."