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A study by researchers at Johns
Hopkins University, Baltimore, Maryland, indicates that the way the body
metabolizes the antiretroviral drug, efavirenz, may cause cognitive impairment
by damaging nerve cells. It had been assumed that the brain damage that occurs
in approximately 50 percent of individuals with HIV was caused by the disease.
Doctors had thought that getting more drugs to the brain would prevent such
impairment. Efavirenz, which is taken as part of a cocktail of medications to
suppress the HIV virus, crosses the blood-brain barrier to reach potential
reservoirs of the virus in the brain and is very good at controlling the virus.
The study led by Norman J. Haughey,
Ph.D., associate professor of neurology at the Johns Hopkins University School
of Medicine, examined blood and cerebrospinal fluid from HIV-infected
individuals enrolled in the NorthEast AIDS Dementia Study. The subjects were
all taking efavirenz. The researchers looked for the levels of the drug and its
metabolites—substances created when the drug is broken down by the liver—and
the effects of metabolites on neurons cultured in the lab. Haughey and his
colleagues found that 8-hydroxyefavirenz, a metabolite of efavirenz, is 10
times more toxic to brain cells than the drug itself, and even in low
concentrations it damages the part of the neurons that allow communication among
brain cells.
Namandje N. Bumpus, Ph.D., another
of the study’s authors, has found a way to modify efavirenz to prevent it from
metabolizing into 8-hydoxyefavirenz, but retain its efficacy in suppressing the
HIV virus.
The study titled, “Dendritic Spine Injury
Induced by the 8-Hydroxy Metabolite of Efavirenz,” was published ahead of print
in the Journal of Pharmacology and Experimental Therapeutics (2012; DOI:
10.1124/jpet.112.195701).
The Friends of AIDS Foundation is
dedicated to enhancing the quality of life for HIV positive individuals and
empowering people to make healthy choices to prevent the spread of the HIV
virus. To learn more about The Friends of AIDS Foundation, please visit: http://www.friendsofaids.org.
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