Common HIV Drug May Lead to Memory Problems
Efavirenz, a commonly prescribed anti-retroviral drug typically used long term by HIV patients, may lead to cognitive impairment, suggests a new Johns Hopkins study.
For a long time, it was assumed that the disease was causing cognitive damage, but Hopkins researchers say efavirenz may be the culprit. Almost half of those individuals with HIV eventually develop some form of brain damage that, although mild, can make it harder to drive, work or participate in everyday activities.
People with HIV are typically prescribed a variety of medications to suppress the virus, and many take the drugs for decades. As one of the few effective drugs that can cross the blood-brain barrier, efavirenz is able to target potential reservoirs of virus in the brain.
Doctors have long thought that it might be possible to minimize cognitive problems associated with HIV by getting more drugs into the brain, but researchers say more caution is needed because of these long-term effects.
“People with HIV infections can’t stop taking anti-retroviral drugs. We know what happens then and it’s not good,” said Norman J. Haughey, Ph.D., leader of the study and 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, samples of blood and cerebrospinal fluid were drawn from HIV-infected patients who were taking efavirenz. Researchers looked for levels of the drug and its various metabolites, which are substances created when efavirenz is broken down by the liver.
Haughey and his team found that one of these metabolites, called 8-hydroxyefavirenz, is 10 times more toxic to brain cells than the drug itself. Even at low levels, this metabolite causes damage to the dendritic spines of neurons. The dendritic spine is the information-processing point of a neuron.
Namandje N. Bumpus, Ph.D., one of the study’s authors, found a way to modify the drug to prevent it from metabolizing into 8-hydroxyefavirenz while still maintaining its ability to suppress the HIV virus.
“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,” said Haughey.
Haughey says that this type of research serves as a reminder that although individuals infected with HIV are living longer than they were 20 years ago, they still encounter significant problems from the drugs used to treat the infection.
“Some people do seem to have this attitude that HIV is no longer a death sentence,” he said. “But even with anti-retroviral treatments, people infected with HIV have shortened lifespans and the chance of cognitive decline is high. It’s nothing you should treat lightly.”
The research is found in the Journal of Pharmacology and Experimental Therapeutics.
Source: Johns Hopkins Medicine
Pedersen, T. (2012). Common HIV Drug May Lead to Memory Problems. Psych Central. Retrieved on May 4, 2015, from http://psychcentral.com/news/2012/10/03/common-hiv-drug-may-lead-to-memory-problems/45478.html