Researcher studies effects of HIV on the immune system

Kushagra Gupta, Staff Reporter

Alan D. Levine studied physics in graduate school and never took a biology class, but now, he is investigating the effects of human immunodeficiency virus (HIV) infections. Levine was the senior author of a study that found that HIV causes patient’s colon to leak dead bacteria into the immune system causing a number of complications.

Levine is studying patients in which the virus’ fatal acquired immunodeficiency syndrome (AIDS) has been mediated using antiviral drugs, but who have other non-AIDS complications.

He found evidence that patients with HIV infections have a permeable intestine, which allowed the dead bacteria residue into the bloodstream. Once in the bloodstream, the immune system mistook the residue as live bacteria and reacted against the dead pathogens. Since the residue kept entering the bloodstream, the patient’s immune systems kept responding, resulting in cardiovascular damage, among other issues.

“Anywhere from 400 to 1000 different species of bacteria live within the colon of the [gastrointestinal] tract,” Levine said.

These bacteria normally provide many benefits to humans, and help to keep them healthy. There is even a new area of medicine devoted to studying how to diagnose and treat people based on the bacteria inside them. However, if the microbes manage to enter the bloodstream in significant quantities, dead or alive, mayhem ensues.

Levine first became interested in studying HIV infected patients during a campuswide effort to study the effects of the infection. In the past, Levine had studied the digestive system, and was attracted to studying HIV due to the similarities that it shared with inflammatory bowel disease, which he had studied in the past. Both diseases can have effects on the immune system and intestine permeability.

He set out to find answers about HIV. He knew that he needed to study the digestive tract of patients who were on antivirals for HIV. Fortunately, many older HIV patients get routine colonoscopies. He was able to get consent to take biopsies from the patient’s digestive tracts.

Levine found that membranes were permeable due to weakened intercellular connections, which allowed dead bacteria to flow past them. From his knowledge studying the digestive tract, he knew that the immune system would react against the residue.

The question that remains is what actually causes the membrane between the inside of the intestine and the blood vessels to break down. It’s simple to point to HIV, but these patients also take antiviral drugs, so those could be the culprit. Because all the patients that are infected with HIV take these drugs, it’s difficult to figure out which to blame. This is the topic of Levine’s future research, which he is hoping to get an National Institutes of Health (NIH) grant for.

He has a couple theories. The first is that, while the virus isn’t replicating in patients on antivirals, it is still present. A similar but more promising theory is that the virus was more pronounced in the patients during initial infection, leading to a lot of damage to the immune system and making the membranes become permeable. Levine’s theory is that they never changed back. His final theory is that it could be a side effect of the antivirals.

Levine came to Case Western Reserve University because he enjoys teaching students and missed the essence of academia. He found biophysics while studying physics for the qualifying exam for his doctorate. As a break, he got up and started roaming the library’s stacks, where he found a journal called Journal of Biophysics.

“There was a paper in there that explained how fluid dynamics can explain how the esophagus works,” he said. “It just so happens that I was studying fluid dynamics that evening for my qualifying exam.”

After that, he was hooked.