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CATIE News - Brain decline linked to cardiovascular disease

2010 Aug 25 - Although HIV infection is generally explained as a virus that damages the immune system, it can also affect many organs and tissues, including the brain. 


While potent anti-HIV therapy (commonly called ART or HAART) can greatly reduce virus levels in the blood, small amounts of HIV continue to be produced within the body's lymph nodes and tissues. This low-level production of HIV causes the immune system to be in an activated state.

The activation of the immune system is a normal response to infection. Once an infection has been brought under control, the immune system dampens down activation. However, because HIV infection persists, the immune system appears to be continuously activated-even in people who use ART for many years. Such prolonged activation may in turn affect a broad range of the body's organs and tissues. This is because the immune system has cells that rove around the body and can take up residence in organs and tissues. There, activated immune cells can affect the surrounding tissues of organs, disturbing the health and functioning of these organs.

Enter the brain

One organ that may be negatively affected by prolonged HIV infection is the brain. Since the earliest days of the HIV pandemic, researchers recognized that, in some cases, HIV infection could eventually result in behavioural and cognitive changes-including difficulty thinking clearly, problems with memory, confusion, delirium, and, in extreme cases, dementia. Now that ART is widely available, AIDS-related dementia is rare in high-income countries. But emerging research suggests that subtle impairment of the brain's thinking abilities occurs even in HIV-positive people who are adherent to therapy and who do not engage in substance use. These findings have spurred further research into HIV's impact on the brain.

No brain is an island

Scientists in high- and middle-income countries who study the brain have been trying to understand the issue of declining neurocognitive ability despite the use of ART and ways to reverse it. One team of researchers has completed its preliminary analysis, which will appear in a future issue of the journal Neurology . The researchers found that, even in people with high CD4+ cell counts, neurocognitive decline was more likely to occur in people with pre-existing cardiovascular disease than in people with traditional risk factors for HIV-related dementia. If this finding is confirmed, further emphasis on improving cardiovascular health for HIV-positive people can be expected.

Study details

As part of a larger study of episodic treatment interruption called SMART, researchers interested in HIV-neurocognitive issues conducted a sub-study with 292 participants from the following countries:

  • Canada
  • Australia
  • Brazil
  • Thailand
  • United States

Participants completed different tests to help researchers understand the brain's ability to solve problems, think clearly, process information and remember. These results were compared to those that had previously been collected from healthy HIV-negative people. Additionally, detailed medical records and results of laboratory analyses of blood were also considered when analyzing the data.

The average profile of participants when they entered the study was as follows:

  • 42% females, 58% males
  • proportion with 12 years education or less - 54%
  • CD4+ count - 536 cells
  • lowest-ever CD4+ count - 225 cells
  • proportion with a viral load of 400 copies/ml or less - 88%


Overall, the researchers stated, neuropsychological testing suggested that people in the sub-study had "below-average performance compared to a healthy [HIV-negative] population." Furthermore, about 14% of participants had more serious neurocognitive impairment. There were no significant differences in neuropsychological test results among different countries.

The researchers found that about one-quarter of participants had depression, with people in Canada, Australia and the U.S. more likely to have depression (41%) than people in Thailand (14%).

Cardiovascular connection

People who entered the study with pre-existing cardiovascular disease were six times more likely to have neurocognitive impairment than those who had no cardiovascular problems. This finding remained even when the study team took into account the following factors:

  • age
  • gender
  • race or ethnicity
  • educational levels
  • country of residence
  • having had AIDS in the past

Furthermore, this six-fold increased risk for neurocognitive impairment was statistically significant.

Other findings: People who entered the SMART study with higher-than-normal levels of total cholesterol or higher-than-normal blood pressure also had a greater risk for neurocognitive impairment.

Oddly, factors that in other studies had previously been linked to neurocognitive impairment-lowest-ever CD4+ count, high viral load, diabetes, or the ability of ART to penetrate the brain-were not associated with this problem in the present sub-study.

Why the connection?

HIV infection is associated with persistent activation of the immune system. An activated immune system releases chemical signals-cytokines-that can adversely affect the health of many organs and tissues, including blood vessels, kidneys and bones.

One previous study found that HIV infection appeared to prematurely age a person's blood vessels 15 years above their current age. This aging of blood vessels may mean that less oxygen- and nutrient-rich blood reaches brain cells. In turn, with poorer blood flow, perhaps fewer waste products are removed from brain cells. These findings may explain the decreased neurocognitive function in the present study with a relatively young population. The study authors note that neurocognitive decline associated with cardiovascular disease does not usually occur in HIV-negative people until they are "at least in their sixth decade."


The present neurological sub-study of SMART has a cross-sectional design. Such studies can only provide a snapshot of people's health at one point in time. Moreover, cross-sectional studies can find statistical associations between factors and events, but they cannot prove cause and effect-in this case, that cardiovascular disease causes neurocognitive impairment.

An advantage of cross-sectional studies is that they are relatively cheaper and faster to implement than a study that monitors a large group of people over many years. The findings from cross-sectional studies are still useful and can be used to formulate studies of a more robust design to explore important research questions.

Bear in mind

Despite the limitations of the present SMART sub-study, its findings are important and echo results of other studies of accelerated aging and HIV. Furthermore, the present study underscores the importance of cardiovascular health not just for the heart but also for the brain.


  1. For tips on understanding and improving cardiovascular health in HIV infection, see CATIE's In-Depth Fact Sheet " HIV and cardiovascular disease: keeping your heart and blood vessels healthy ," available at:
  2. The Winter 2010 issue of CATIE's Positive Side magazine features a first-person article by activist Maggie Atkinson on the topic of neurocognitive problems in HIV. You can read about her experience and what she learned about protecting her brain in " A Mind of Her Own," which can be found at:

-Sean R. Hosein


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  10. Wright EJ, Grund B, Robertson K, et al. Cardiovascular risk factors associated with lower baseline cognitive performance in HIV-positive persons. Neurology . 2010; in press .
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CATIE-News is written by Sean Hosein, with the collaboration of other members of the Canadian AIDS Treatment Information Exchange, in Toronto.

From Canadian AIDS Treatment Information Exchange (CATIE). For more information visit CATIE's Information Network at


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