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Alberta: Factors Predictive of HIV-Related Neurocognitive Impairment

December 11, 2012

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Different Risk Factors

Taking many factors into account, the following were significantly linked to an increased relative risk for developing symptoms of HIV-neurocognitive impairment:

  • Length of Survival
    Researchers found that for every year of being HIV positive, there was a 7% increased relative risk for developing symptoms of neurocognitive dysfunction. This does not mean that every year 7% of people developed these problems. Rather, it means that the risk increased by 7% for every year that participants survived. Note that the relative risk for an event can eventually exceed 100%. Again, this does not mean that 100% of people will develop a certain problem, just that the relative risk for it exceeds 100%.
  • Age
    For each year of increase in age, there was a 3% increased relative risk for developing symptoms of neurocognitive problems.
  • CD4+ Cell Count
    Previous studies have found that the lowest-ever CD4+ cell count (the nadir CD4+ count) has been linked to an increased risk for developing neurocognitive problems. In the present study, for every one-cell decrease below the average nadir (174 cells) there was a 0.4% increase in the relative risk of developing symptoms of neurocognitive dysfunction.
  • Pre-Treatment HIV Viral Load
    Participants whose HIV viral load at the start of the study was greater than one million copies/ml had a relative risk of developing neurocognitive problems that was five-fold greater than those participants whose pre-treatment viral load was less than 1,000 copies/ml.


Bear in Mind

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  1. A European study called Cascade also studied possible risk factors for HIV-related dementia in the present era. The Cascade dataset included 15,308 HIV-positive participants, 222 of whom developed dementia. Similar to the Alberta team, researchers working with Cascade also found that factors such as older age and longer duration of being HIV positive were linked to an increased relative risk for developing neurocognitive dysfunction.
  2. Two other studies have found that increased years of education appears to reduce the risk for developing neurocognitive dysfunction.

In the Alberta study, researchers found a statistical trend toward an increased risk for developing symptoms of neurocognitive dysfunction among participants who were less educated. However, this trend did not become statistically significant, perhaps because the numbers of participants in the study was insufficient.

This issue of the size of the study may have affected the Alberta researchers' ability to detect associations between factors such as a history of substance use and hepatitis C virus infection and the subsequent risk for developing symptoms of neurocognitive dysfunction.


Applicability

Overall, the Alberta researchers stated that their findings can be used to help care teams in other HIV clinics decide which HIV-positive patients require screening for neurocognitive problems.


Next Steps

Now the Alberta researchers as well as other teams working in the field of neurocognitive research need to study ways to prevent and treat HIV-related neurocognitive dysfunction.


Acknowledgement

We thank infectious disease specialist John Gill MD, PhD, for his research assistance, helpful discussion and expert review.


Resources


References

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  2. Haase AT. Perils at mucosal front lines for HIV and SIV and their hosts. Nature Reviews Immunology. 2005 Oct;5(10):783-92.
  3. McCombe J, Vivithanaporn P, Gill M, et al. Predictors of symptomatic HIV-associated neurocognitive disorders in universal health care. HIV Medicine. 2012; in press.
  4. Heaton RK, Clifford DB, Franklin DR Jr., et al. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology. 2010 Dec 7;75(23):2087-96.
  5. Spudich S, Gisslén M, Hagberg L, et al. Central nervous system immune activation characterizes primary human immunodeficiency virus 1 infection even in participants with minimal cerebrospinal fluid viral burden. Journal of Infectious Diseases. 2011 Sep 1;204(5):753-60.
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  7. Vivithanaporn P, Nelles K, DeBlock L, et al. Hepatitis C virus co-infection increases neurocognitive impairment severity and risk of death in treated HIV/AIDS. Journal of the Neurological Sciences. 2012 Jan 15;312(1-2):45-51.
  8. Heaton RK, Franklin DR, Ellis RJ, et al. HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature and predictors. Journal of Neurovirology. 2011 Feb;17(1):3-16.
  9. Appay V, Sauce D. Immune activation and inflammation in HIV-1 infection: cause and consequences. Journal of Pathology. 2008 Jan;214(2):231-41.
  10. Gendelman HE, Zheng J, Coulter CL, et al. Suppression of inflammatory neurotoxins by highly active antiretroviral therapy in human immunodeficiency virus-associated dementia. Journal of Infectious Diseases. 1998 Oct;178(4):1000-7.
  11. Harezlak J, Buchthal S, Taylor M, et al. Persistence of HIV-associated cognitive impairment, inflammation, and neuronal injury in era of highly active antiretroviral treatment. AIDS. 2011 Mar 13;25(5):625-33.
  12. Bhaskaran K, Mussini C, Antinori A, et al. Changes in the incidence and predictors of human immunodeficiency virus-associated dementia in the era of highly active antiretroviral therapy. Annals of Neurology. 2008 Feb;63(2):213-21.
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This article was provided by Canadian AIDS Treatment Information Exchange. It is a part of the publication CATIE News. Visit CATIE's Web site to find out more about their activities, publications and services.
 

 

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