Results from a small study indicate that certain regions of the brain become significantly smaller in people with HIV. The findings also show that this reduction in brain size occurs even when the HIV infection is well controlled with antiretroviral therapy.
“What we saw was that HIV does affect the brain, and it shrinks areas of the brain,” said Dr. Beau Ances, an assistant professor of neurology at Washington University at St. Louis and lead author of the study. “These areas were just as small in HIV-positive individuals who were and who were not on [antiretroviral] medications,” he added.
Results from the study also suggest that age and HIV infection independently lead to lower brain volumes.
“In particular, we looked at an area that’s very deep in the brain, called the caudate nucleus. We know that the caudate nucleus, which controls some motor movement and planning, is sometimes affected with HIV. We saw that there was an effect of HIV and that there was an effect of aging, but no interactions between them. It looked like HIV aged the brain by about 15 or 17 years or so,” said Dr. Ances.
According to the study authors, results from this exploratory study suggest that administration of neuro-protective therapy may help prevent brain damage in HIV-positive individuals. Dr. Ances noted that the drugs selegeline (Deprenyl, Carbex), minocycline, and valproic acid (Depakote) are neuro-protective agents that have been tested in people with HIV. Results so far have shown no improvement, but he pointed out that starting treatment earlier, before any significant impairment, may be beneficial.
Dr. Ances also noted that previous studies have shown that antiretroviral drugs differ in their ability to reach and penetrate the brain. “HIV gets into the brain and stays in the brain. Are there ways that we could get more of the antiretrovirals into the brain so that we could knock down the virus?” said Dr. Ances. He added that trials are under way to determine the effects of higher and lower penetrating antiretrovirals on brain structure and function.
However, the authors cautioned that larger studies in people with acute and chronic HIV infection are required to more thoroughly understand the effects of HIV on the brain.
Dr. Ronald Ellis, an associate professor of neuroscience at the University of California, San Diego, who was not involved in the study, added that physical exercise might help maintain brain function. “There is a growing body of evidence in non-HIV infected individuals showing that physical exercise benefits the brain. And for that reason, people with HIV may consider using exercise as a way to preserve their brain structure and function,” he said, though he cautioned that this conclusion was speculation.
Previous studies have shown that HIV infection can affect brain function, resulting in lower cognition (see related AIDS Beacon news). In addition, several factors such as aging, vitamin B12 deficiency, or a stroke can lead to the death of nerve cells in the brain, resulting in brain shrinkage (called atrophy).
According to the study investigators, toxic products made by the virus are thought to cause much of the damage observed in the brain. However, the authors noted that HIV-positive individuals continue to show evidence of brain shrinkage and dysfunction despite the advent of highly active antiretroviral therapy (HAART).
As a result, several aspects of HIV infection may be involved in brain impairment. For example, it is possible that long-term exposure to antiretroviral drugs, such as Sustiva (efavirenz), could have toxic effects on nerve cells in the brain. In addition, as the immune system recovers during antiretroviral therapy, brain cells may experience immune-mediated damage.
In this study, researchers aimed to understand the individual effects of HIV infection, HAART, and age on brain size and function. The authors also investigated whether changes in brain volume can serve as a reliable indicator of structural damage in the brain.
A total of 78 individuals participated in the study. A third were HIV negative, a third were HIV positive but had never been on HAART (HAART naïve), and a third were infected and on HAART.
The researchers recorded several HIV-related parameters for each participant, including time since infection, viral load (amount of virus in the blood), and current and lowest recorded (nadir) CD4 (white blood cell) counts.
The average age of HIV-positive, HAART-naïve individuals was 37 years old. About 92 percent were male, and the average duration of HIV infection was three years.
The average age of HIV-positive individuals on HAART was 40 years old. Nearly 85 percent were male, and the average duration of HIV infection was 10.5 years.
HIV viral load was lower and CD4 counts were higher in individuals taking HAART compared to HAART naïve participants. However, the lowest recorded CD4 counts were lower in participants on HAART, possibly due to a longer average duration of infection.
The authors used magnetic resonance imaging (MRI) to estimate the volume of specific regions of the brain. Participants’ responses to a set of questionnaires were used to assess their cognitive function.
After recording initial measurements, 46 percent of the HAART-naïve participants started HAART and all parameters were recorded again after six months of antiretroviral therapy. This data was used to assess the short-term effect of HAART on the brain.
Results from the study showed that HIV-positive individuals performed worse on neuro-psychological tests, as compared to uninfected individuals. Among the HIV-positive participants, HAART-naïve individuals and those taking HAART performed comparably on the tests.
MRI data also showed that HIV-positive individuals, regardless of their HAART status, showed significant reduction in the volume of three specific brain regions – the amygdala, the corpus callosum, and the caudate.
The amygdala is thought to be important in the processing of emotional reactions. The corpus callosum helps the left and right halves of the brain to communicate with each other, and the caudate is involved in learning and memory.
The researchers found that the caudate volume was affected by both HIV and aging. They estimated that HIV infection was associated with a 6 percent reduction in caudate volume for each decade of infection, while aging was associated with an additional 4 percent reduction per decade.
The authors estimated, using modeling techniques, that the caudate volume likely declines gradually for about 13 years after HIV infection, after which it reaches a steady state. Overall, they concluded that the effects of HIV infection on caudate size are equivalent to those of 17 years of aging.
When HAART was introduced in HAART-naïve individuals, viral loads were significantly reduced and CD4 counts increased after six months of therapy. However, the authors observed no change in caudate volumes.
For the corpus callosum and the amygdala, only HIV, and not aging, had an effect on size. Study participants with HIV had a corpus callosum that was an average of 8 percent smaller than participants without HIV, and an amygdala that was an average of 7 percent smaller.
There was no association between reduction in brain volume and viral load or current or lowest CD4 counts. The researchers noted that this result contradicts those from previous studies, which suggested that brain impairment is associated with low nadir CD4 counts (see related AIDS Beacon news).
For more information, please refer to the study in the Journal of Acquired Immunodeficiency Syndrome (abstract).
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