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Williams' Insights About Key Molecule Advance HIV Research

For The Heights

Published: Sunday, September 30, 2012

Updated: Wednesday, January 9, 2013 18:01

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Alex Gaynor / Heights Staff

In the research laboratory of biology professor Ken Williams, research on a molecule has been used to make the connection between the immune response of the human body and the increasing prevalence of cardiovascular disease in patients living with Human Immunodeficiency Virus (HIV).

This molecule, known as CD163, is a scavenger receptor that is released upon the activation of monocyte and macrophage cells during the human body’s response to the HIV infection. PET imaging showed that there was macrophage infiltration into diseased arterial walls and these macrophages were positive for and can shed a soluble form of CD163.

Williams has worked with HIV research in the past, having done work at McGill University and the Montreal Neurological Institute, Dartmouth College, and Harvard Medical School on the subject of dementia related to the HIV virus. He has seen the research and the knowledge about the disease progress as more research is done.

“In the first 10 to 20 years, it was all about T cells. Early on, we didn’t find out as much about HIV, but we learned a lot about T cell immunology,” Williams said.

Research on anti-retroviral drugs now has allowed patients to live longer with the HIV virus, which is for the most part undetectable. Many revolutionary new developments, including the combinations of anti-retroviral drugs, have changed the lifestyles of those with HIV.

“Now we’re at the point in this country where we’ve gone from single-drug use to treating those at high risk for HIV prophylactically, before they’ve even been infected,” Williams said.

With medication that can allow those infected with HIV to live longer, new medical issues are being seen.

Sixty percent of people with HIV have cardiac problems. “These are people with non-traditional risk factors,” Williams said. “We know from this that it’s related to HIV.” Furthermore, neuropsychological problems are also likely associated with problems from blood vessels, a result of long-term infection.

In addition to cardiac problems, more HIV patients are observed to be developing dementia. “The presence of dementia is increasing, and that’s because people are living longer,” Williams said. “People with AIDS live longer, and those effects are coming out.”

The research performed in Williams’ laboratory gives new information about the connection between the immune system, HIV, and potential antiretroviral therapies. Macrophages and monocytes were shown to be connected to the debilitating diseases faced by those infected with HIV. These effects are faced despite treatment with anti-retroviral therapies, which are able to stop the progression of HIV.

A large number of HIV patients show non-calcified coronary atherosclerotic lesions. These lesions increase with the markers of macrophage activation, showing the link between HIV and cardiac disease. The recently published report in The Journal of the American Medical Association (JAMA), however, demonstrates using PET macrophages directly in the ascending aorta.

The research team also included Tricia Burdo, research assistant professor of biology, and Harvard Medical School researchers Sharath Subramanian, Ahmed Tawakol, Suhny Abbara, Jeffrey Wei, Jayanthi Vijayakumar, Erin Corsini, Markella V. Zanni, Udo Hoffman, Janet Lo, and Steven K. Grinspoon.

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