� 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 Neurology (www.aan.com). 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 brain. 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 dementia.� �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 medtrib@medtrib.com