� 1999 Medical Tribune News Service
Use of antiretroviral therapy reversed HIV-related dementia in a study of
16 patients. This is the first study to show that the early stages of this
dementia can be treated and reversed with antiretroviral therapy.
�We saw a dramatic reversal of the initially abnormal brain chemistry,�
said Linda Chang, M.D., associate professor of neurology at the University
of California, Los Angeles, and senior author of the study, which was
published in the September 11 issue of Neurology (1999;53:782-789
[www.neurology. org]), the scientific journal of the American Academy of
The therapy, called the �HIV cocktail,� or HAART (highly active
antiretroviral therapy), is a combination of three or more medications,
including: a protease inhibitor, such as indinavir; a nucleoside reverse
transcriptase inhibitor, such as zidovudine (AZT); and a non-nucleoside
analog, such as nevirapine, that prevents the virus from multiplying.
During the later stages of AIDS, 20 to 40 percent of patients develop
cognitive abnormalities, including memory loss and difficulty
concentrating. Although dementia is more common later in the disease,
symptoms can sometimes be seen early on, said Dr. Chang, who is also
affiliated with the Harbor-UCLA Medical Center.
Some of the proteins on the HIV virus are believed to be toxic to neurons
and inflict direct injury on the brain. The brain�s inflammatory response
to HIV may also hasten neurological damage.
Both before and after antiretroviral therapy, the researchers studied 16
HIV patients, all of whom were well into the course of the disease and who
showed beginning signs of mental decline. Patients were tested using
clinical ratings of dementia. In addition, brain scans were taken using
proton magnetic resonance spectroscopy. With this test, the investigators
evaluated chemical markers in the frontal lobes and basal ganglia, regions
associated with dementia. Test results of these patients were compared
with those of 15 HIV-negative volunteers.
Before the therapy, the HIV patients had elevated levels of myoinositol, a
compound present in glial cells, which appear at the site of neurological
insult. On clinical rating scales, patients also showed mild levels of
dementia. After three to nine months of antiretroviral treatment, the
patients� dementia ratings went from mild to very slight. Their levels of
myoinositol also decreased.
With antiretroviral therapy, �the patients improved clinically and their
brain chemistry normalized,� Dr. Chang said.
Two of the HIV patients, however, experienced side effects of nausea,
headache and diarrhea. After these patients stopped antiretroviral
treatment, they experienced further cognitive impairment, and levels of
chemical markers of brain damage increased.
In the report, the authors expressed concern that some newer
antiretroviral medications, such as the protease inhibitors, do not cross
the blood-brain barrier, leaving HIV infection relatively untreated in the
However, because the brain-scanning procedure is non-invasive and has no
side effects, Dr. Chang said, in the future it can be used repeatedly to
determine long-term outcomes of HIV therapies on dementia. �The patients
we looked at were at the very early stages of the dementia,� explained Dr.
Chang. �We don�t know what we�d see if they were at the end stage of
�It�s not surprising that mixing AZT and some of the new drugs together
offers people some relief from dementia,� said Gregg Gonsalves, policy
director of Treatment Action Group (www.aidsinfonyc.org/tag), a New York
organization that advocates more research efforts directed at finding a
cure for AIDS.
Gonsalves expressed concern that because many HIV patients become
resistant to drug treatments, sometimes even after a year of therapy,
these people will not be able to combat either the physical or mental
effects of HIV. �We still need better drugs to treat HIV, especially ones
that aren�t cross-resistant with existing ones on the market, and we need
ones that get through the blood-brain barrier,� he emphasized.
October 7, 1999
� 1999 Medical Tribune