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Expecting the unexpected

Myron Cohen has spent the past 40 years helping to recruit the most promising infectious disease experts from across the nation to build a program at Carolina that’s become a leader in HIV. That expertise is now being used to tackle COVID-19.

Researcher works with pipettes at the lab bench
Research technician Katherine Sholtis works in the Margolis Lab of the HIV Cure Center in the Genetic Medicine Research Building on November 15, 2018, on the campus of the University of North Carolina at Chapel Hill. (Johnny Andrews/UNC-Chapel Hill)

Whoosh, whoosh, tick. Whoosh, whoosh, tick.

Soft morning light bathes a man in a white-clad bed. As his chest slowly rises and falls, the rhythmic whirring continues — the sounds of a mechanical ventilator helping him breathe. Eyes open, he looks exhausted but grateful. Hopeful. He survived another night.

Before arriving in this place, he experienced a slow progression of symptoms: a dry cough, chest tightness, shortness of breath, and fever. The last pushed him to visit the hospital, where his symptoms worsened, and his lungs began to fail him. Within hours of arriving, doctors intubated him.

This experience is one many have endured recently. But this is not the present day. This is not COVID-19. It is, though, the start of an epidemic that would change the world forever. The year is 1982. The man suffers from pneumocystis pneumonia, and doctors have just diagnosed him with a previously unheard of disease that’s slowly infiltrating the population: AIDS.

Like most hospitals, UNC-Chapel Hill saw its first AIDS cases in the early 1980s. At the time, nearly three-quarters of the people diagnosed with the immunodeficient disease contracted PCP. In 1984, researchers from the Pasteur Institute in Paris discovered HIV as the virus that causes the disease.

One year later, about 15 to 20 percent of all admissions to UNC Hospitals were for AIDS. These patients were placed in a special ward that now serves people with COVID-19. Some of the nurses within the ward are the same ones who helped with the HIV epidemic, said Myron Cohen, director of the UNC Institute for Global Health and Infectious Diseases.

Since HIV became a pandemic, more than 75 million people have been infected with the virus and about 32 million have died from AIDS, according to the World Health Organization. Thirty-eight million people are still infected worldwide.

Today, HIV researchers have another nasty virus to contend with: SARS-CoV-2. To date, nearly 12 million people have been diagnosed with COVID-19, half a million people have died worldwide, and one-quarter of those deaths have been in the United States.

But there is much hope — in part, thanks to Carolina’s prowess in the field of HIV.

“Virtually every HIV expert on this campus has been assigned or repurposed, in one way or another, to work on COVID-19,” Cohen said, “because they are able to deal with emerging pathogens after dealing with HIV for 30 to 40 years.”

Of the top 10 universities conducting the most HIV research in the world, Carolina places at number three, a designation the university has achieved thanks to years of hard work across all aspects of the field, from prevention to vaccine development and, ultimately, a cure.

Changing behaviors

In 1981, while conducting medical evaluations as part of UNC Hospitals’ consultation service, Cohen walked into an exam room to find a young, feverish man with hemophilia — a blood disorder that prevents clotting — whose lymph nodes were about the size of a small fist. Doctors tested him for cancer, but the results came back negative. The patient’s health continued to deteriorate at a rapid pace.

This must be AIDS, Cohen thought.

After assessing the severity of the man’s symptoms, hematologist Gil White requested permission to send one of the man’s lymph nodes to a biomedical researcher at the National Cancer Institute. Cohen’s guess was soon confirmed.

The man soon passed away and, within months, UNC Hospitals’ 30-bed AIDS ward filled to capacity. Between 1981 and 1984, more than 50% of the nation’s hemophilia population who received treatments through blood transfusion became infected with HIV.

The beginnings of the HIV epidemic created fear across America. Where did it come from? How does it spread? Who is most susceptible? In response, the federal government placed an AIDS brochure in every mailbox in the nation in 1988.

Other early-stage efforts to tackle HIV encouraged changes in sexual behavior like condom use and the closure of “hotspots” like bathhouses. While these endeavors marked the start of slowing the spread of HIV, it would take much more to halt it altogether. But first, researchers needed to learn more about how the virus works.

Evolving with the virus

HIV is a retrovirus, meaning it invades a host’s DNA and replicates within its cells. This makes it incredibly hard to find and fight. Even more complicated is the fact that HIV can evolve to hide within the body and infect different cell types. At first, the virus targets CD4-positive T cells, a type of white blood cell responsible for immune response. But when that cell supply gets low, the virus searches for a new home to live in.

That evolution is what Ronald Swanstrom studies. For a long time, Swanstrom worked on protease inhibitor resistance. Protease is an enzyme involved in the maturation of the virus during assembly, allowing it to become infectious and spread. If you can inhibit protease activity, you can prevent the replicating virus from infecting other cells. While there are more than five protease inhibitors on the market, they must be taken in combination with other antiviral drugs to halt HIV infection.

“Otherwise, the virus begins to mutate and figures out how to keep growing in the presence of the inhibitor,” explained Swanstrom, who adds that understanding these basic biological processes helps improve treatments for the disease.

Swanstrom also researches how the virus gets inside of and functions within the brain — a place with minimal CD4-positive T cells, meaning the virus must learn to adapt there by infecting different cell types. The virus travels to the brain within immune cells and is then forced to evolve for survival. While HIV infections in the brain are often only recognized late in the disease, it’s vital look for the virus here, as it can cause a slew of neurocognitive problems and, in extreme cases, dementia. HIV-associated dementia occurs in approximately 25% of people with untreated HIV infection.

“HIV launches an ongoing battle between the virus and the body — and the virus has the advantage that it can evolve rapidly,” Swanstrom said. “So the more we understand what those evolutionary signatures are, the more we understand that interaction between the virus and the host.”

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