Dementia: Brain Damage Found in HIV Patients on Antiretroviral Therapy
January 16, 2004
Researchers from the San Francisco Veterans Affairs Medical Center (SFVAMC) used a combination of MRI brain imaging, electrical brain activity recording and behavioral tests to compare the brains of HIV-positive people on antiretroviral (ARV) therapy with the brains of healthy subjects. They found significant damage in the brains of HIV-positive patients whose viral load was effectively suppressed by ARV therapy.Adapted from:
"The results of our study raise the concern of brain injury in HIV subjects who are on treatment, even among those who are virally suppressed," noted study senior investigator Michael Weiner, PhD, who is affiliated with SFVAMC and the University of California-San Francisco. "What we don't know is whether or not these changes occurred some time ago, prior to effective treatment, or whether these changes represent ongoing injury."
Symptoms of HIV brain damage may include depression, memory loss, slow mental and physical response time and sluggish limb movement. Such symptoms can progress to a severe disorder, HIV dementia, that afflicted some 20 percent of HIV patients before the advent of ARV therapy. Dementia patients may experience severe memory loss and cognitive impairment, tremors, hyperactive reflexes, immobility and loss of speech.
The research team compared 39 HIV-positive people who had been taking ARV drugs for at least 3 months with 39 uninfected control subjects. The HIV-positive group was subdivided into a virally suppressed group whose 16 members had no detectable virus in their blood, and a viremic group whose 23 members had substantial virus in blood samples. Participants ranged in age from 25-57 years old. All had from 12-20 years of education, and no one with a history of substance abuse or psychiatric or neurological disorders was included.
The biggest difference the investigators found come from contingent negative variation (CNV) brainwave recordings, which charted the magnitude of brainwaves during a computer task performance test. While CNV activity among HIV-negative participants surged shortly after the appearance of the first image, it remained nearly flat among both groups of HIV-positive subjects. Lack of CNV response generally indicates damage or destruction to brain cells of the basal ganglia, part of the brain that coordinates motor behavior and one of two areas where HIV tends to concentrate.
Testing reaction time, the study found that among controls, the stronger their CNV activity, the faster their response time. Despite their flat CNV activity, HIV-positive participants had equally good response time, suggesting that their brains may have compensated by creating other pathways than the normal neurological linkages.
The investigators found reduced caudate nuclei -- a substructure of the basal ganglia -- in HIV-positive patients, as well as smaller volume of the thalamus, which serves as a relay station for sensory information.
On several behavioral tests, there were no differences among the three groups. However, viremic HIV patients scored significantly lower than virally suppressed participants and the controls on three tests.
Although it is not known whether any or all of the damage occurred before patients started ARV therapy, even minor damage should serve as a warning, said Linda Chao, PhD, the study's lead author. Weiner said follow-up studies are needed to assess HIV patients over a longer time period to determine whether injury is ongoing.
The study, "Abnormal Contingent Negative Variation in HIV Patients Receiving Antiretroviral Therapy," appeared in Neuroreport (2003;14(16):2111-5).
This article was provided by CDC National Prevention Information Network. It is a part of the publication CDC HIV/Hepatitis/STD/TB Prevention News Update.