The retrovirus that causes AIDS acts like a shape-shifting villain. As HIV replicates over time, random mutations take place in the viral genome—one of the hallmarks of the disease that makes containing and curing it such a challenge.

“We’ve been very interested in studying viral evolution and the structure of the virus, from the beginning, most earliest stages all the way through the end, when someone dies from immune system dysfunction, the virus in the brain, with neurologic problems,” says Brian Wigdahl, chair of the Department of Microbiology and Immunology and the director of the Institute of Molecular Medicine and Infectious Disease.

In a $3.5 million NIH-supported research project, Wigdahl focuses on what happens to the replication process as patients live longer thanks to combination drug therapy. His lab also is interested in how the virus affects the aging process.

To study these issues, blood samples from a large group of patients—more than 500 people—seen at Drexel’s HIV/AIDS clinic will be analyzed over time. (It is the largest clinical population being monitored long-term in the Philadelphia area, Wigdahl says.)

“We’ve taken HIV disease and with antiretroviral drug therapy, we’ve converted it into a chronic condition.”

In this project, his hypothesis is that viral and host genetic factors account for aging AIDS patients’ susceptibility to neurocognitive problems. “My interest is starting to really characterize the molecular architecture of the viral genome,” he says. “It’s a study of detail.”

But the payoff is potentially huge, Wigdahl says. It could lead to therapies targeted at new viral genes and proteins, including those related to cognitive decline. Even though about 30 drug treatment protocols for AIDS already exist, “it is still important to keep developing new therapies because of drug resistance and toxicity,” he says.

Wigdahl, who has studied HIV/AIDS since the mid-1980s, also still holds out hope for finding a cure. “That’s a major point of emphasis with a number of groups, including our own,” he says.

In the U.S., more than 1.1 million people are living with HIV infection, according to the Centers for Disease Control. Researchers estimate that by 2015, half of the infected population will be older than age 50.

“It’s a good problem to have,” Wigdahl says. “We’ve taken HIV disease and with antiretroviral drug therapy, we’ve converted it into a chronic condition.”

In response, his research is shifting gears from a younger population of study to an older one, with a focus on how AIDS will progress in that aging environment, where normal declines in the immune system (immunosenescence) and cognitive performance are already underway.

One area of investigation is viral single nucleotide polymorphism, or the genetic variation in a DNA sequence. A person with HIV infection has thousands of viral cells, each with a slightly different genetic makeup, the so-called viral swarm. But interestingly, during the early hours up to a few weeks after initial transmission from one individual to another, “a serious bottle neck occurs,” Wigdahl says. “What really gets transmitted to that individual is a single genotype.”