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closer examination of this target needed with improvement treatment options!
Nov 23, 2003

Dr. Young,

As you note, hiv therapy has drastically improved the outcomes for the majority of positive individuals. Nevertheless, this articles raises some concern about the fact that some brain damage does occur even with individuals on therapy. Is this because we haven't produced drugs yet that can pinpoint the virus in every avenue? Are we getting better at this and how are researchers at work to pinpoint this concern?

Thank you.

Michael

Medical News HIV Infection May Cause Neurological Damage Regardless of Antiretroviral Therapy Effectiveness, Study Says HIV infection may cause damage to the brain even if the virus is suppressed to nearly undetectable levels with antiretroviral therapy, according to a study published in the Nov. 14 issue of the journal NeuroReport, the San Francisco Chronicle reports. Researchers from the University of California-San Francisco departments of psychiatry and radiology at the Veterans Affairs Medical Center conducted a battery of tests on 31 HIV-positive patients and 35 HIV-negative patients to gauge neurological damage (Russell, San Francisco Chronicle, 11/14). The researchers used neuropsychological tests and magnetic resonance imaging to test the patients' brain structure and functions (Chao et al., NeuroReport, 11/14). The researchers also tested patients' contingent negative variation amplitude -- a measure of a person's overall ability to react to something by taking physical action. Among the HIV-positive patients, both the participants who were taking antiretroviral drugs and the participants who were not taking antiretrovirals showed poor results, suggesting that they may have damage in the basal ganglia part of the brain. In addition, MRI scans showed that HIV-positive participants -- regardless of their therapy regimen -- had possible damage in the thalamus area of the brain (BBC News, 11/17). The problem of AIDS-related dementia, which once affected one in five AIDS patients, was thought to have been largely solved with the advent of antiretroviral drugs (San Francisco Chronicle, 11/14). "You see people on [antiretroviral] medications and they seem fine," Dr. Linda Chao, lead author of the study, said, adding, "But the take-home message is that antiviral medications might not be stopping brain damage. When we put patients' brains under closer scrutiny, we saw that they were affected."

Blood-Brain Barrier Many antiretroviral drugs are ineffective at lowering viral levels in the brain because they cannot get past the blood-brain barrier, a filter designed to protect the brain from large, potentially dangerous molecules, according to BBC News. Theoretically, people on antiretroviral therapy may have higher levels of HIV in the brain than in the rest of the body even though they may have nearly undetectable viral levels in the rest of the body (BBC News, 11/17). However, the level of neurological damage detected in patients on antiretroviral therapy is so low that it requires sophisticated equipment and tests to detect, Dr. Michael Weiner, director of the MRI unit at the VA medical center and a lead investigator in the study, said, adding, "Patients do not appear to be clinically affected." However, Weiner said that further study is needed because it is unknown whether the abnormalities detected were caused by HIV or by the antiretroviral drugs, according to the Chronicle (San Francisco Chronicle, 11/14).

Response from Dr. Young

Michael- thanks for your posting and attention to the literature surrounding HIV.

This study does raise important questions about therapuetic goals-- some have asserted that getting medications to all anatomic sites is an essential goal. The fact is, that not all meds get into the brain or spinal fluid with equal ease. This has not stopped medications that seem to get to the nervous system from being potent and even improving persons who have HIV-related nervous system disease, so the link between drug penetration and clinical improvement is not absolute.

I do think that we are getting better at the whole thing, but perhaps, as the article suggests, this is not a time for complacency. BY



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