11 November 2011 - Although the widespread availability of potent combination therapy for HIV infection (commonly
called ART or HAART) greatly prolongs the survival of people, it does not rid the body of HIV. Moreover, despite treatment, subtle
changes to the immune system caused by HIV persist. One of these changes may be unnecessary activation of the immune system. As
cells of the immune system are dispersed throughout the body, persistent immune activation over many years has the potential
to weaken organs.
One organ that is the focus of particular concern is the brain. In the time before ART was available in high-income countries,
an extreme and devastating form of neurocognitive decline called dementia was feared by HIV-positive people. Although ART has
made HIV-related dementia uncommon, several studies have found that subtle cognitive dysfunction may be relatively common
in HIV-positive people, even those who are highly adherent to ART. Some researchers and HIV-positive people worry that
mild neurocognitive impairment today may pave the path for more severe neurocognitive impairment as HIV-positive people age.
A team of researchers in the U.S. has been monitoring the health of several thousand women, some who have HIV and others who
are at high risk for infection with HIV. They conducted preliminary neurocognitive assessments and extensive monitoring of the
overall health of women in their study, particularly cardiovascular health.
As cardiovascular disease grows worse, the carotid arteries, which supply oxygen-rich blood to the brain, can become clogged
and narrowed because of sticky deposits called plaque, made from debris and cholesterol. As a result of the buildup of plaque,
less blood flows to the brain. The researchers assessed the health of the carotid arteries. They found that, in general,
HIV-positive women had poorer neurocognitive test results and that these were linked to poorer cardiovascular health.
Their findings, if confirmed in a long-term study, raise the possibility of future clinical trials to prevent or
treat cardiovascular disease so that neurocognitive functioning in HIV-positive people, particularly women, may
be maintained or improved.
As part of the Women's Interagency HIV Study (WIHS), researchers enrolled 3,766 women, both HIV positive and HIV negative, in the
following six American cities:
- the Bronx
- Los Angeles
- San Francisco
- Washington, DC
Every six months, participants were extensively interviewed and underwent physical exams and other health assessments. By
collecting data from these participants on a regular basis, a large dataset has accumulated. From time to time, researchers
analyse the information that has amassed to learn about trends in different aspects of HIV-positive women's health. This
CATIE News bulletin focuses on a neurological sub-study of WIHS that enrolled 1,282 women, distributed as follows:
- HIV positive: 891 women
- HIV negative: 391 women
For the neurological sub-study, ultrasound scans of the carotid arteries (in the neck) were performed along with some
The study team did not provide a complete profile of the volunteers in the neurological sub-study, but we do know that
the women were, on average, around 41 years of age.
The research team found that, in general, HIV-positive women had poor neurocognitive test results compared to HIV-negative women.
This difference appeared to be influenced by poorer cardiovascular health among HIV-positive women.
A sticky growth called plaque, made up of LDL-cholesterol and cellular debris, can build up along the wall of arteries. Over
many years plaques can increase in size and impede the flow of blood as arteries narrow and become less flexible. As less
blood flows, tissues become starved of oxygen and nutrients; as a result, they do not function as well and can even die.
In the present study, researchers found that the buildup of plaque in the carotid artery and a narrowing of the carotid artery
were linked to worse neurocognitive function. This negative effect of cardiovascular disease was profoundly significant. Indeed,
the research team commented that the effect of cardiovascular disease on neurocognitive impairment in symptom-free participants
was akin to the decreased neurocognitive function they had seen in people with AIDS.
In general, the team did not find that specific classes of anti-HIV drugs had a significant impact on neurocognitive functioning.
Future studies need to be designed to properly assess this, as there is at least one study suggesting that the anti-HIV drug
efavirenz (Sustiva, Stocrin and in Atripla) is associated with a degree of neurocognitive impairment.
The WIHS neurologic sub-study confirmed findings from another sub-study, from a clinical trial called SMART. However, the SMART
neurologic sub-study had only 122 HIV-positive women.
The WIHS study, with its focus on HIV-positive women just entering middle age, is important because it has found an association
between carotid artery disease and neurocognitive impairment. Among HIV- negative people, such impairment does not usually
appear until at least 15 years later, according to the WIHS team.
Don't press the panic button
It is important to note that the present study design was cross-sectional. That is, assessments were generally done at one
point in time rather than many points over several years. Cross-sectional studies cannot provide definitive answers to
important scientific questions. However, they are a first step to establishing that there is a problem and they lay
the foundation for undertaking studies of a more rigorous nature.
Also, comprehensive neurocognitive assessments were not performed in the present study. Therefore, its findings are not definitive
and should not be a cause for alarm.
Why such early artery problems?
As HIV is a chronic infection, it causes continuous and excessive inflammation that affects the immune system. Anti-HIV therapy
is not able to completely suppress this excess inflammation. Over the long term, particularly if risk factors for cardiovascular
disease are present (such as smoking, substance use, poor diet and being overweight), the harmful effect of these risk
factors on overall health, especially cardiovascular health, is likely amplified by HIV infection.
Back to the brain
Studies on neurocognitive impairment in HIV-positive women who are monitored over several years need to be done, and in the
future such studies should do at least the following:
- continue to assess the cardiovascular health of both middle-aged and older women
- be comprehensive, include MRI (magnetic resonance imaging) scans and explore the functioning of different parts of the brain
- extend the present study's findings
If the findings from the WIHS neurological sub-study are confirmed in a longitudinal study, it might be possible to reverse neurocognitive impairment in some HIV-positive women by dealing with issues related to cardiovascular health. This possibility should not be surprising because among elderly HIV-negative people who have a buildup of plaque and narrowing in their carotid arteries, interventions-usually surgery-to reverse this have helped improve cognitive functioning. Note that such surgery can sometimes have adverse effects. However, if carotid artery disease is caught early in HIV-positive people, before serious symptoms appear, then safer means of improving cardiovascular health-quitting smoking, changes to the diet, aerobic exercise and treating co-morbidities such as diabetes, high-blood pressure and kidney disease-could be tested for their impact on neurocognitive impairment.
-Sean R. Hosein
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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 http://www.catie.ca
Source: CATIE: CANADIAN AIDS TREATMENT INFORMATION EXCHANGE