Inside the Mind of a Leader: What’s Next for Infectious Disease Medicine?

Click the play button to watch now:

Subscribe: Apple Podcasts | Amazon Music | Spotify | iHeart Radio

Welcome to the Science at UH podcast, sponsored by the University Hospital's Research and Education Institute, where we explore breakthrough research, clinical innovations, and the science of transforming patient care and health outcomes.

I'm your host, Dr. Daniel Simon. Thank you for joining us for another episode.

Daniel Simon, MD: Today, I am happy to welcome our guest, Dr. Ighoho Ofotokun, who recently joined University Hospitals as Chair of the Department of Medicine and Physician-in-Chief of our health system.

Dr. Ofotokun is a highly accomplished and internationally renowned clinician, mentor, and clinical and translational infectious disease researcher. Dr. Ofotokun has authored over 250 scientific publications, his work has earned him numerous awards and recognition. He is an elected member of the National Academy of Medicine, the recipient of the 2024 Maxwell Finland Scientific Achievement Award from the National Foundation of Infectious Diseases.

Welcome, Igho.

Ighovwerha Ofotokun, MD: Thank you.

Daniel Simon, MD: Igho Yu grew up in Nigeria and eventually became a leading HIV researcher in the US. What early experiences or influences shaped your interest in HIV, infectious disease, and in global health?

Ighovwerha Ofotokun, MD: First and foremost, thank you so much, Dr. Simon, for inviting me to this podcast. I want to say that it's been a wonderful experience transitioning from Emory to University Hospitals. Thank you so much for your leadership in the community. I'm grateful for the warm reception that I have received from many people across the healthcare system.

To respond to your question, I would say among the many things that influenced the trajectory of my career, two stood out. First, as you noted, I grew up in Nigeria, and during my early education, I think in my 5th grade, I was exposed to the history of West Africa.

As many of you will be aware, it was a rich history of strong empires, brave rulers and kings such as the Benin Empire, the Mali Empire, the Ashanti Empire, manuscript from the historic library of Timbuktu still exists till today. It was also a history of dark period of slavery, the unimaginable suffering and hardship inflicted on Africans. After the slave trade, however, came many missionaries and people of goodwill who started schools, hospitals, community centers, eradicated diseases, improved health and well-being for the people. Many of the missionaries were doctors and nurses.

My young mind in those days, in elementary school, just couldn't really factor on how the same people that brought so much suffering, and hardship could also bring this amount of goodness. So that was the way my 10-year-old brain was thinking, and then it occurred to me that people can choose what they do with their lives. You could choose to do good, you could also choose otherwise, and I saw medicine as a tool for good. And that was when I actually began to really gravitate; my interest in medicine arose. And that was really what made me pursue a career in medicine. So at that time, there was nobody in my family that had been a doctor. Other than being taken to the doctor, I don't even know anybody personally that was a physician. And so, this realization really influenced my decision to go to medical school.

When I was in medical school, after I finished college and I went to medical school, a second thing happened, the AIDS epidemic. And so, at this time in Africa, as many of you would remember, this was the early 90s. The epidemic was very devastating. And so, when I finished my medical training, I became a medical officer at the Mission Hospital in the Niger Delta of rural southern Nigeria. There, we had no treatment for AIDS; most people that came to us died. The only thing we had was treatment of opportunistic infection, septra and fluconazole, that is Bactrim. And there was a lot of stigma around the disease.

So many men in particular, because of the stigma, would not come for care. And a lot of women came because they wanted to live for their children and they wanted to live for their families. But we had nothing to offer. Many of them succumbed to the infection and left behind offering their children. So, this experience was foundational to my career and continued to influence the trajectory of my career in medicine to this day.

Daniel Simon, MD: Wow, that's just incredibly inspirational that, as you said, you made that choice for good. And that medicine was the outlet for you to do that. So, take me through, you're there, just as I was a resident in the onset of AIDS and HIV, and we felt helpless. And clearly over time, we became more hopeful, and it was obviously a transition to antivirals and other therapies.

Tell me a little bit about the highlights of some research milestones in your own career that you'd like to share with us. What do you think has been real difference makers in HIV from you and your teams that you built together?

Ighovwerha Ofotokun, MD: Great question.  Again, when I finished my training in Nigeria, I became a medical officer. I transitioned from Nigeria to the United States. I went to University of Michigan in Ann Arbor to do my residency and also my fellowship. And again, the death that I saw with HIV, the suffering, and the fact that we couldn't do much about it really stuck with me. And that really gravitated the trajectory of my career towards HIV, especially HIV as it affected women and children. And so, when I finished my training at Michigan, I eventually became a faculty at Emory. And one of the things I wanted to do in addition to providing care for people living with HIV was to develop a research career that will help alleviate the suffering people living with HIV, to make the treatment more tolerable, to look at the complication of living with long-term, living with chronic HIV infection. A lot of my work was really tailored towards improving patient outcome in that area. So, I'll give you an example.

So in 1996, antiretroviral therapy, the highly active antiretroviral therapy, became available. And when I started my practice at Emory in the early 200s, the choice of antiretroviral therapy were limited to two major regimens. One of them included a drug called efavirenz. The other regimen included a drug called atezanivir. The challenge with those two regimens, they were very effective but they were not suitable. They were not ideal for women of childbearing age. The efavirence regimen had teratogenic potential. The artisanovir regimen was associated with jaundice, yellowness of the skin. So, it created a cosmetic challenge for young women of reproductive age. And so, we then came up, how do we come up with a regimen that will save life, but without the added challenges for young women.

So, we came up with this simple study, what was then known as the ACTG5257 study. It was a large study to identify a regimen that is safer for women of reproductive age. That study tested a new class of drug, then known as the integrase strand inhibitor. And at the end of the study, it was the largest of its type; we had it in 52 centers across the United States, recruited one of the largest population and included significant number of men and women diverse population. And we were able to, at the end of that study, to come up with a regimen that we found that was really effective for the treatment of women without the added toxicity. And that study was the beginning of the launch of the integrase strand inhibitor in the treatment of people living with HIV.

Today, that regimen is the gold standard. It became incorporated into the guideline, the US guideline, the WHO guideline, and is now the first line regimen for treatment of people living with HIV in the world.

Daniel Simon, MD: Wow, that's just, again, an amazing contribution, Igho.

There's unfortunately, scientific times are tough now, the cuts to USAID do pose significant threats to global health research activities. Maybe you could tell us a little bit about your groundbreaking global research partnerships that included collaboration with France to really establish an international epidemiology database in Lagos in Nigeria, in which you were focusing on serving as a West African site. Can you tell us a little bit about what do these global health studies teach us and how are they relevant to treating HIV potentially in the US?

Ighovwerha Ofotokun, MD: So first of all, we were very intentional when we were building our research portfolio. And so, when I started out early in my career, we had one intention, first to develop a strong base here in the United States and then expand internationally.

So, it was part of the vision we had, that we were going to build a thriving research portfolio that is domestic and then leverage that as a platform to expand to other parts of the world. And so that was how we started. We focused on HIV-related comorbidities.

So, remember, at the time when I started my career, antiretroviral therapy was becoming widely available. People were no longer dying of the epidemic. The drugs were effective. They had toxicity and so the thought that we had then was that we're not able to completely eradicate the virus. And living with the virus over a prolonged period of time is like to have some other consequences. People were not thinking of this at that time because we just felt that if you were going to take the drug every day for the rest of your life and the virus is going to remain in your body for the rest of your life, not completely eradicated, it would have long-term complications. And so that was how we built our study around the aging-related comorbidities as people living with HIV.

And so, once we developed our robust study here in the US, we then developed relationship with people outside of the US. We wanted to take our study to Africa, where the bulk of the epidemic was, and started studying people to see what we were seeing here in the US was the same, whether there were differences or whether there are nuances we could learn from looking at other settings. And so that was kind of how we started our work in Africa and during the course of our work, NIH took notice of some of the progress we were making.

And then they were actually the one who linked us up with the collaboration with the University of Bordeaux and we became part of this bigger network, the International Epidemiological Database for AIDS. So, it's a big international network that included almost all the regions of the world, but our work was focused in West Africa, Nigeria, and seven other West African countries.

And the idea was to collect data prospectively, over a period of time, to continue to understand the impact of HIV as people ages with therapy and suppression of the virus. And some of the things that we have learned from that experience was, just like we see in the United States, in Africa and other parts of the world, people have many of the aging-related comorbidities. So, HIV leads to what we call premature aging, so that you see, many of the aging-related conditions, such as cardiovascular disease, neurocognitive disease, bone disease, fracture, occur at a much earlier age in people living with HIV compared to the general population. Even though they are treated, they are virologically suppressed, and they are not as sick as they were during the early era when we didn't have treatment.

One of the things we did was that we also leveraged the platform to build capacity in the countries where we were working. We had training grants, the NIH Faculty D43 program, and within that training grant, we were able to empower people in the country to also apply. We trained them to apply for their NIH funding. And so, we built a small investment of less than $1,000,000 a year within a period of five years into an investment of over $20 million, where most of the work is being done on the ground by people that we have trained in those countries.

And I think those are some of the skills that I hope to bring to my experience here at the University Hospitals, particularly the ROE Green Center for Travel Medicine and Global Health and the work that is being done at Uganda through the Roe Green Center at the University Hospitals. We're hoping that we can join forces with all of the people here at UH and help build that program into a world-renowned program that is self-sustaining.

Daniel Simon, MD: So Igho, you participated in the earliest stages of a global pandemic, HIV. And then in the last couple of years, you've been a leader in our second major pandemic, which is that of COVID-19, and specifically the really troublesome problem of post-infectious complications that we call long COVID.

Tell us a little bit, you've led this incredible national effort, the adult cohort of the RECOVER trial, nearly a billion-dollar effort to understand long covid, and you're one of the leaders. Tell us a little bit about what have we learned about long covid from this study?

Ighovwerha Ofotokun, MD: This is one question that is being increasingly asked in the field of infectious diseases. So, this concept of infection-associated chronic condition, or post-viral syndrome, as you have alluded to, and as a matter of fact, recently I was asked by the leading journal in the field of infectious diseases, the Journal of Infectious Diseases, to write a perspective on this topic.

So, the basic concept of post-viral syndrome or infection-associated chronic condition, it's simple. So, the way we are thinking about this is that when there's an acute assault to the body, so if there's an acute viral infection such as COVID-19, what happened is the body immune system is activated. So, it sends message to other parts of the body, many of the metabolic pathways, and also to the energy centers in the brain and it tells the body to slow down, to shut down. And then the energy, the resources, so to say, are then used to attack, to quell the acute infection. And so, when that acute period is over, the immune system then sends another message to tell the body, we've taken care of the problem.

Now go back to your normal operating status. But for some individuals, for reasons that are not clearly understood, they are not able to - so the energy system does not wake up; the metabolic pathway does not return to normal. And so these result in a number of abnormalities, what we call viral persistence, immune dysregulation and chronic inflammation, dysregulation of the coagulation pathways, autonomic dysfunction, autoimmune disorders that we now see manifest as post-viral syndrome, and in the case of COVID-19, as long COVID. So that is the simple theory that we are working with.

And so, this phenomenon is not unique to SARS-CoV-2 virus infection. It's something that we have known before now in HIV, in flu, in enteroviruses. What is different is the scale of the pandemic. So this virus, the pandemic affected almost everybody. And so if you only have 1% of people that are affected by COVID-19 developing long COVID, that is a huge number of people when you're thinking of millions, almost billions of people that are affected by the epidemic in the world. And why this is important is that not just we don't only now need to think about the acute phase of an infection, but we also, for example, today we estimate that almost 25% of cancer are related to acute viral infection. So as physicians or infectious diseases physicians, we not only now think of treating the five or seven days of the virus, but we need to then at what group of people, what are the risk factors that people are likely to have that we precipitate them to having long-term sequelae, like we see with long COVID.

And so, one of the things we're doing in the RECOVER study is to use COVID, SARS-CoV-2 infection and long covid, to understand this phenomenon of post-viral syndrome and to see.. are there risk factors? Are there predisposing factors? Are there things that will predispose people to develop this sequelae of acute viral infection? So that is one of the things we're doing in the RECOVER study. In addition to understanding the pathobiology of the current long COVID conditions and to look for target for treatment and also for prevention.

Daniel Simon, MD: I'm so glad that people like you and Grace McComsey and others are tackling this problem, which clearly affects, as you point out, millions of people worldwide.

As a cardiologist, we are very concerned. There's about 100% increase in heart attack in the year following a COVID infection. And there's about a 200% increase in blood clots and pulmonary emboli. So we face it in our practice. We're very concerned when patients who have established coronary disease have a COVID infection. And so thank you for all the work that you're doing. Just one final question; and I think we're only going to be able to skim the surface of this and we'll bring you back.

You are an exceptional academic leader. We are so lucky to have recruited you from Emory to the warm climate of Cleveland. And I understand that you're living very close to Lake Erie, so we almost have an ocean for you as well. So, we're going to think that it's warm and we won't worry about the snow. But you're coming to lead the largest department at UH Cleveland Medical Center. You have almost 350 faculty members. Tell us just in a few minutes, what do you think are the top two or three things that you want to do out of the gate. I know that you have a lot of plans and it's a five-year plan, but what's really burning for you to do out of the gate?

Ighovwerha Ofotokun, MD: Thank you so much, Dr. Simon. I consider it a privilege, a honor to assume this role. You've been around for some time and you know that University Hospital as a whole is about its community. It's about Northeast Ohio, about the health of people in Cleveland. And the primary focus of the department under my leadership is really to continue to play its part, to support the University Hospital System to accomplish this dream, this vision of continuing to provide the best care it can to our community.

And one of the things we're thinking about, if you look at the way the healthcare system is structured, the Department of Medicine is the gateway department. People come in into the system mostly through the department. People touch, patient touch the system through the department. And many of the people that leave the hospital also leave through the Department of Medicine. And so what we are hoping to do, just the broad philosophy, is to position the Department of Medicine as the gateway department within the healthcare system. And what that means is that we want to take a lead.

So many of the metrics that we're interested in medicine, whether it's quality of care, expanded access to the entire healthcare system, the culture of growth, improvement in outcome, scholarship, innovation, discovery, and education, a loft of that happens within the Department of Medicine. So, our goal is to really change the culture, to let everybody know that this is the gateway department, and we have to set the standard, a good standard, and to meet all of those metrics that we are interested in, ultimately to improve the care of our community.

And like I have discussed with you before, the first step we're taking is really to build our operational mechanics, to empower our leaders, the vice chair, associate program director, the division directors, to take bold leadership decision to really position us as a good gateway, a good representative of the healthcare system. And then we're also trying to identify some of those gateway initiatives.

Diabetes, for example, for over half of our patient population are affected by diabetes in one way or the other, either pre-diabetes or post-diabetes. We want to develop our healthcare system to be a leading center of excellence, an NIH-designated center of excellence for diabetes, so that people can come to us. If they come to us for their diabetic care, if half of the population of Cleveland see us as a place to come for their diabetic care and we do a good job, they would also come for other things. Same thing for chronic disease management. It's a big issue, and there are several of them…COPD, heart failure…what we want to do is to develop a model for the country of really managing a chronic disease condition across the healthcare system.

It's not as easy as you said. How do you manage a population of people with congestive heart failure when there are limited physicians to do that? So, what we want to do is to work with the quality officer, Peter Pronovos, and others to really think through the model of chronic disease management. And then again, make our department a designated PCORI or AHRQ center for the development, for the management of a chronic condition.

And the last example I will give, and I think this is an example that is sometimes underestimated, is our travel medicine. Think about it, 18 million people travel to Cleveland every year. And over 10 million people pass through the Cleveland Hopkins Airport every year, over 10 million people. Assuming we're able to attract just 1% of those people to receive their travel care at our center, that will be over 300,000 people that will touch on us. So, the point here is that get people to come in. If they come in for one thing and they see how well we do, they will come in for all of their other care.

So that is really this gateway phenomenon. To be a good gateway for people to come for their medical care, their sub-specialty care, and then refer us to surgery, referrers to ophthalmology, referrer to dermatology. So that is really the way we're looking at this, and we want to be good custodian of that gateway entrance into the university hospitals.

Daniel Simon, MD: That's just a phenomenal vision. I want to help you get there, and so we'll be talking frequently. I want to thank you for taking the time to speak with us today, Ego. This has been just fantastic talking to a superstar in the infectious disease space, manning 2 pandemics now, HIV and COVID-19. It's a real privilege and honor.

To learn more about research at University Hospitals, please visit UHhospitals.org/UHResearch.

Thank you, Ego.

Ighovwerha Ofotokun, MD: Thank you.