Why does HIV infection cause dementia in some patients and not in others?
With help from a new 5-year, $3.7 million federal grant, UC San Diego clinician-researcher Dr. Davey M. Smith is looking for the answer.
He and his coworkers will study HIV in a total of 1000 HIV-infected patients in Brazil, China, India, Romania, and the U.S.
In these five countries, three major subtypes of the HIV virus are found.
His latest study, funded by the National Institute of Mental Health, will look for the causes of AIDS dementia in HIV subtypes from five countries (in red on the map above).
Dr. Smith hopes to find out which HIV subtypes, or clades, are more likely to cause neurological damage, and why the affected individuals are susceptible.
Dr. Smith is an Assistant Professor of Medicine in the Division of Infectious Diseases. He joined the faculty in 2003 as a clinician and translational researcher.
He learned in January that the National Institute of Mental Health had decided to fund his study. The title is “A Multi-site Investigation into the Effect of HIV Clade on Neurocognitive Impairment.”
It’s the first study of its kind.
“There’s a need to compare the HIV subtypes in their genetic makeup and their effect on the brain,” Dr. Smith says. “Most of it is still an open question.”
The HIV found in the rest of the world
is very different from that
in the U.S. and Europe.
“Everything we know about the way HIV affects the brain is based on the HIV virus that’s found in the United States and Europe,” he says. “The HIV found in the rest of the world is very different.”
HIV mutates rapidly as it enters new environments, both in the world and in the human body. Not only is HIV in China different from HIV in Romania; HIV in an individual’s brain is different from the HIV in his or her blood.
“HIV is one of the most diverse organisms, if not the most diverse organism we have,” Dr. Smith says. “It’s a hundred times more diverse than influenza.”
Researchers are just beginning to understand the genetic variations of HIV and how they affect the way the virus is transmitted.
Dr. Smith has developed a way to inspect the HIV virus for its genetic signature, a pattern of mutations in the HIV gene.
In the new project, he and his team will use that technique to compare the genetic makeup of HIV in blood versus brain, in individuals with and without neurological damage, in the five countries.
Researchers will look at
the “genetic signature” of HIV
across the world.
The study is an example of translational research, which is a high priority at UC San Diego and in the Department of Medicine.
“UCSD is a great place for doing translational research, applying basic science to clinical problems,” Dr. Smith says. “There’s very strong support for it here.”
“The HIV research team,” he adds, “is a really great group of people.”
Dr. Smith joined the faculty in 2003 after training at UC San Diego in both internal medicine and basic and clinical research. After his internal medicine residency training and a term as Chief Resident, he completed a fellowship in Infectious Diseases and a Masters of Advanced Studies (M.A.S.) in Clinical Research here.
He is Medical Director of the San Diego County Early Intervention Program at the Antiviral Research Center (AVRC).
He directs two co-infection clinics at the Veterans Administration San Diego Healthcare System (VASDHS), one for HIV/Hepatitis C and one for HIV/HPV infection.
He conducts his clinical research at the AVRC and his basic science studies in his UC San Diego campus laboratory.
“UCSD is a great place
for doing translational research.”
His advisor and mentor is Dr. Douglas D. Richman, Professor of Pathology and Medicine and the Florence Seeley Riford Chair in AIDS Research.
Dr. Richman is Director of the UC San Diego Center for AIDS Research (CFAR).
Another HIV researcher whom Dr. Smith considers a mentor is Dr. Joseph K. Wong, now Associate Professor in the Division of Infectious Diseases at UC San Francisco and a staff physician at the San Francisco Veterans Affairs Medical Center.
As both a clinician and a translational research virologist, Dr. Smith divides his time between the laboratory and the patient clinic.
“It means a lot to me,” he says, “to be able to do both patient care and research.”
His goal, both in the laboratory and in his clinics, is to provide better care for individuals who are infected with HIV.
“It’s good to see people getting better
and going on in their lives.”
On a recent trip to Ethiopia, Dr. Smith saw HIV-infected patients who had not had access to the antiretroviral treatments we have here in the U.S. and Europe.
“Seeing them reminded me of where we were in the early 90’s here,” he said. “It was heartbreaking; HIV is so destructive. We have got to do better in getting our antiretroviral therapy out there.
“But we’re getting there,” he says. “It’s good to see people getting better and going on in their lives. It’s good to see things change.
“That perspective, I think, makes me a better researcher,” he says. “I get to see the why. Why this research is so important.”
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