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CATIE - www.catie.ca

CATIE News - HIV and the brain-aging and other issues

2011 Jan 12 - When the AIDS pandemic began in the early 1980s, researchers noticed that some affected people also had neurologic problems. Although HIV does not appear to infect brain cells (neurons), this virus does infect cells of the immune system-T-cells and macrophages-and as these cells enter and leave the brain, they can unwittingly carry HIV with them.

Once inside the brain, HIV-infected T-cells and macrophages release viral proteins that trigger inflammation and injure neurons. If this injury accumulates, it can affect a person's ability to coordinate their muscles and movement, slow down learning, cause problems thinking clearly and affect concentration, memory and speech. In some cases, personality changes can occur. In extreme cases, severe forms of the previously listed problems can occur, affecting a person's ability to look after him or herself. This is called HIV-associated dementia.

Thanks to the widespread availability of potent anti-HIV therapy (commonly called ART or HAART) in high-income countries, HIV-positive people who receive regular monitoring and are on treatment are expected to live for decades. Furthermore, HIV-associated dementia is now uncommon among ART users.

Emerging issues

HIV infection activates the immune system and causes inflammation. Although levels of HIV and inflammation are reduced by anti-HIV therapy, ART is unable to cure HIV infection. Researchers are concerned that persistent inflammation may slowly degrade many organ-systems, including the brain.

Here are some research questions that scientists grapple with when they conduct HIV-related neurological research:

  • Will HIV-positive people face an increased risk of neuro-degenerative disorders such as Alzheimer's and Parkinson's diseases as they age? Preliminary results suggest that so far there is no increased risk for Alzheimer's disease and that premature onset of Parkinson's disease is rare in HIV-positive people. However, long-term studies are needed in these areas.
  • HIV infection appears to accelerate the aging of the cardiovascular (CVD) system. As blood flow-which carries oxygen and nutrients-is vital to the brain, does accelerated CVD aging affect the workings of this organ?
  • As a result of ART, HIV-associated dementia is now rare. However, increasingly there are reports of subtle neurocognitive deficits in some ART users. Doctors in high-income countries have had complaints from some HIV-positive people of mild memory problems and difficulties with concentration, planning and multitasking despite the use of ART. Who will and will not be affected by this? Are the declines in neurocognitive functions reversible?
  • Also in high-income countries, syphilis has become a relatively common sexually transmitted infection, particularly among some sexually active gay and bisexual men, some of whom are co-infected with HIV. Shortly after they gain entry to the body, treponemes-the germs that cause syphilis-can invade the brain and spinal cord. Does HIV infection intensify syphilis-related damage to the brain (and other organs) or vice-versa?

In several upcoming CATIE News bulletins we report research on some of these issues.

-Sean R. Hosein

REFERENCES:

  1. Ances BM, Christensen JJ, Teshome M, et al. Cognitively unimpaired HIV-positive subjects do not have increased 11C-PiB: a case-control study. Neurology. 2010 Jul 13;75(2):111-5.
  2. Agrawal L, Louboutin JP, Marusich E, et al. Dopaminergic neurotoxicity of HIV-1 gp120: reactive oxygen species as signaling intermediates . Brain Research . 2010 Jan 8;1306:116-30.
  3. Gelbard HA, Dewhurst S, Maggirwar SB, et al. Rebuilding synaptic architecture in HIV-1 associated neurocognitive disease: a therapeutic strategy based on modulation of mixed lineage kinase. Neurotherapeutics. 2010 Oct;7(4):392-8.
  4. Poletti M, Baldacci F, Nuti A, et al. Decision-making impairment in a patient with new concomitant diagnoses of Parkinson's disease and HIV. Journal of Neuropsychiatry and Clinical Neurosciences. 2009 Summer;21(3):352-3.
  5. Tisch S, Brew BJ. HIV, HAART, and Parkinson's disease: co-incidence or pathogenetic link? Movement Disorders . 2010 Oct 15;25(13):2257-8.
  6. Schouten J, Cinque P, Gisslen M, et al. HIV-1 infection and cognitive impairment in the cART-era: a review. AIDS . 2011 ; in pre ss.

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


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