HIV study asks BYU biologist to help

Though it is the fourth leading cause of death worldwide, researchers have yet to develop an effective vaccine for HIV/AIDS, but a researcher at Brigham Young University is working to speed the process along.

Keith Crandall, chairman of BYU's biology department, was asked by researchers working on clinical trials for a new AIDS vaccine to participate in analyzing some of their work.

"Our lab has been working on HIV evolution questions for 15 years now. We've done the research, published the papers and worked on the methodology. They knew our research and asked us to participate," he said.

The recent study was the first comprehensive survey of genetic variation of HIV across the country.

"It was really surprising to me that no one had done such a thing. You would think the CDC (Centers for Disease Control and Prevention) would be interested in it, because you have to understand what's out there in order to make a reasonable vaccine against it."

The data they were involved with collecting more than doubled the number of full-length DNA sequences for the disease in the national genetic database, he said.

Researchers working on the vaccine's phase three clinical trial also wanted to see how effective the vaccine was, if at all, and how much protection it could afford. To do that, the study enrolled patients at a high risk for getting HIV who didn't actually have the disease, then tested them every three months over an extended period of time.

"When they became HIV positive, you knew they had contracted the disease within the past three months," Crandall said. "Usually studies of HIV patients involve those who actually have the symptoms of the disease, and that often doesn't happen for seven to 10 years. The immune system is pretty good at beating back the virus, at least initially."

Crandall and his colleagues sequenced a portion of the DNA from the virus that was collected from 349 patients who had recently been infected. They found no evidence of different evolutionary patterns in the virus between those taking the placebo and those receiving the vaccine.

"We knew from the efficacy trial that the vaccine didn't have an impact, but we were hoping when we looked at the molecular level the vaccine might be driving its evolution," which didn't happen, he said.

In the process, he and his researchers developed some powerful analytical approaches to compare the DNA sequences of those infected with those who weren't infected. Those research methods have established something of a new "road map" for similar analyses of other AIDS vaccine trials. The new approach is reported in the journal Molecular Biology & Evolution.