Big Tent, one team

How a multidisciplinary research partnership built to fight HIV, Ebola and other infectious diseases turned its people, expertise and experience to fight COVID-19.

A group of doctors standing outside a building.
Before the COVID-19 pandemic, Dr. Emily Ciccone, a fellow with Carolina's Division of Infectious Diseases, worked in Uganda studying respiratory illnesses in children with staff of the Kasese Health Centre (left to right) Emmanuel Baguma, field site coordinator; Michael Matte, researcher; Jethro Muliro, lab technician; Rabbison Muhindo, program manager, Miriam Businge, research assistant; Edgar Mulogo, Mbarara University of Science and Technology/UNC collaboration co-founder; Moses Ntaro, researcher; Erisania Muthegheki, nursing officer (kneeling); Lydia Kabugho, study coordinator; and Ciccone.

Carolina’s Pandemic Year: This week last March, the University shifted to remote instruction. The Well is marking the occasion with a week of special stories, including reflections from Chancellor Kevin M. Guskiewicz, predictions from Carolina’s faculty on lasting changes to post-pandemic life and, below, ways the University has addressed the crisis.

People dying in great numbers around the world. A race to discover prevention and treatments, sometimes leading to dead ends, but sometimes leading to life-saving medicines.

Sounds like 2020, right?

A similar crisis arose in 1983, one year shy of researchers identifying the human immunodeficiency virus (HIV) as the cause of AIDS. Infectious disease doctors at Carolina were in the early stages of treating patients with the disease and learning about it. One of those doctors was 30-year-old Myron Cohen.

Dr. Myron Cohen smiles while facing the camera.

Dr. Myron Cohen

Dr. Cohen, Yeargan Bates Professor of Medicine, Microbiology and Immunology, would go on to lead the Division of Infectious Diseases for 30 years and equip an interdisciplinary research infrastructure that in 2007 became the Institute for Global Health and Infectious Diseases. That moment formalized an already strong partnership forged in the crucible of infectious diseases with the division and Carolina’s schools, departments and centers.

In 1992, a young virologist, Dr. Joe Eron, joined the division and soon discovered a passion for clinical trials and clinical care that led to key discoveries in HIV research. In 2019, Eron took over as division chief. The Herman and Louise Smith Distinguished Professor of medicine has been influential in Carolina’s extension and enhancement of research, care and prevention around the world, particularly as much of the research switched to COVID-19 prevention and treatment.

Since those early days, discoveries, research and patient care around the world positioned the institute to ramp up quickly in the search for treatments for COVID-19.

Today, U.S. News and World Report ranks UNC-Chapel Hill 11th among infectious diseases programs globally. But that’s only one measure. More important measures  — in lives saved, medicines discovered, suffering eased, jobs created and local economies improved — demonstrate the global importance of the partnership among the University’s researchers, physicians and committed workers on all levels.

The institute covers four continents, with flagship programs in the African countries of Liberia, Malawi, South Africa and Zambia; China and Vietnam; Nicaragua; and the U.S. Its researchers have completed more than 500 clinical trials and studies in their fight against a wide array of infectious diseases, including COVID-19, which has killed more than 2.6 million people worldwide.

Early days: focusing on HIV/AIDS

Cohen came to Carolina in 1980 to study white blood cells and the bacteria gonorrhea. Infectious diseases was a smaller specialty at the time. When HIV/AIDS numbers rose rapidly, the division grew as the need for treatment and research increased.

“So many people with hemophilia were exposed to HIV,” Cohen said. “We hired lots of people in medicine and public health and other departments in the mid-’90s to do research on HIV and work in other countries, including countries in southern and eastern Africa in particular.”

Dr. Joseph Eron

Dr. Joseph Eron

After Eron was hired to run the HIV clinic, “his leadership skills quickly became obvious,” Cohen said. Eron took over HIV treatment research and built the program, along with the late Dr. Charlie van der Horst and Dr. David Wohl.

Eron and Cohen hired the best faculty and staff, many of whom have stayed at Carolina. Cohen said that longevity in the faculty has been critical to building a world-class clinical trials unit, starting at a time when few drugs existed to treat HIV.

Today, the ideas, resources and opportunities have converged into a highly collaborative culture supported by key tenets of intellectual generosity, shared leadership, a Big Tent philosophy and a common mission.

Intellectual generosity

Among those tenets, Eron holds high what he calls intellectual generosity.

“If someone does something, they get the credit for it,” Eron said. “Intellectual generosity helps keep our group together.”

It’s a concept that he understands through personal experience. “A memory that strikes me so much is that at the beginning of doing HIV research, we were fortunate enough to participate in the first trial of the HIV cocktail, the thing that made all the difference.”

Eron ran the trial at the behest of senior investigator van der Horst. Study results published in 1998 in the New England Journal of Medicine indicated that the “HIV cocktail” of drugs indinavir, zidovudine and lamivudine effectively treated HIV. It was ground-breaking news.

The study sponsor wanted to include van der Horst as the lead Carolina investigator because he directed the HIV clinical research team. Instead, van der Horst insisted that Eron receive credit for running the trial, contrary to the practice of including senior investigators as study authors, regardless of their role in a study.

“Charlie was so intellectually generous,” Eron said. “In my career, I’ve tried to be the same way. It’s not easy because the urge is to take credit for everything. But that’s how it should work.”

With that lesson in mind, Eron uses his Twitter feed to highlight his colleagues’ successes.

Dr. Ada Adimora.

Dr. Ada Adimora

In some ways, that type of generosity stems from what Dr. Ada Adimora describes as collegiality. “What’s really unique about the institute is the way the collaborative nature of the relationships we have enables all the diverse types of research by really brilliant people,” said Adimora, the Sarah Graham Kenan Distinguished professor of medicine.

Adimora, who researches sexual behavior and sexually transmitted infections, including HIV, remembers former division chief Dr. Fred Sparling encouraging her shortly after she joined the division to write a handbook for clinicians on sexually transmitted diseases. “It was based on a textbook co-authored by Dr. Sparling and Dr. King Holmes. He gave me that opportunity. I was able to hone my writing skills and begin networking with some of the senior researchers in the world,” Adimora said.

“That collegiality and encouragement are really critical factors in the success of the institute,” she said.

Shared leadership

Cohen and Eron bring their own styles to leading the division and institute.

The University’s associate vice chancellor for global health and medical affairs, Cohen is known for his work on transmission and prevention of HIV. He is the architect and principal investigator of the multinational HIV Prevention Trials Network 052 study confirming that antiretroviral treatment prevents the sexual transmission of HIV-1. Under his guidance, the division grew from 10 to more than 50 faculty physicians.

Angela Kashuba. Photo by Jenna Miller.

Angela Kashuba. (Photo by Jenna Miller.)

Angela Kashuba, dean of Carolina’s Eshelman School of Pharmacy, said that Cohen gets everyone aligned and moving in the same direction. “He is focused on building teams to work on big ideas.”

Eron, an expert in clinical trials and observational data, is known as a humble leader who wants everyone to understand the reasons for clinical trials and who provides constant feedback on the importance of each person’s role. In leading faculty, he steps back to let them do what they do best — generate ideas.

He is an internationally recognized researcher, teacher and clinician, who treats people living with HIV at UNC Medical Center’s Infectious Diseases Clinic. Eron also directs the UNC Center for AIDS Research Clinical Core and is principal investigator for the UNC Global HIV Prevention and Treatment Clinical Trials Unit (UNC Global HIV CTU).

“We want to look at each study and say, ‘This is what we’ve learned here. Here’s how you have made a difference. Our group worked together to change things here. Look, the survivors are better with this treatment. You contributed to this.’ I want them to take those messages and understand them,” Eron said.

That understanding helps when things may not go well.

Susan Pedersen, lead study coordinator for the UNC Global HIV CTU, said, “One of the things we’ve learned is that it’s almost impossible to not have a mistake now and then. With the right people in place, it will happen infrequently and it will be self-correcting, not a continuing trend. And people of the quality that we have are so invested that you don’t really have to retrain them. They have already learned from the mistake and have figured out immediately how not to make the same mistake again.

Susan Pedersen

Susan Pedersen

“It’s easy when you have people who always are trying to do things perfectly. The hardest part about managing staff is supporting them when a mistake happens because they’re their own hardest critics. A lot of our job is telling people ‘It’s OK. No one can get through years of clinical research and not make a mistake.’”

There have been failures along the way. “One of the early failures is when we didn’t have the respect for or understanding of what clinical coordinators did, the people who were on the ground, enrolling participants and collecting and entering the data,” Eron said.

Instead, doctors without research experience were enrolling patients and entering information into a study database. “That was a mistake because we didn’t really have respect for the type of training and effort required to accomplish that work.”

Now, Eron said, “We have well-trained nurse coordinators and research assistants who are critical to the work on infectious diseases. They enroll participants, get consent, follow up by phone. They screen medical records and find the optimal people for our studies. Our data staff are meticulous with data entry and rapidly address queries. We’ve learned to respect expertise and to maximize strength and minimize weaknesses.

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