Greg Bisson left for Botswana five years ago as an ambitious young epidemiologist with plans on making a real contribution to the massive fight there against HIV and AIDS.

But when Bisson actually met with the clinicians struggling to treat Botswana’s millions of AIDS patients, he found that his presence wasn’t necessarily welcomed. At best, he remembers, he was viewed with skepticism.

“It was almost like you had been invited into somebody’s home after there had been some huge tragedy,” says Bisson, a senior scholar in Penn’s Center for Clinical Epidemiology and Biostatistics and an assistant professor of medicine and epidemiology in the Department of Medicine. “It’s not the most comfortable interaction.”

The problem, Bisson says, was that by the time he arrived, Botswana was home to scores of other university researchers who, just like him, were trying to offer something to the anti-AIDS effort.

It was just that the on-the-ground doctors—the ones treating up to 50 patients a day to try and get the epidemic under control—simply didn’t see what good those researchers were doing, at least not in the short term.
It’s safe to say the clinicians who once harbored such doubts about Bisson, and his work, have changed their minds.

Over the past few years, Bisson has emerged as one of the most accomplished and important researchers in his field, authoring two key studies that are already helping doctors more easily track, and more effectively treat, the millions of patients receiving life-saving antiretroviral therapy.

Q. Tell me about your background.
A. I was a Midwesterner, born in Minnesota. As a kid, I was always interested in foreign cultures and faraway places. Sometimes in those long Minnesota winters, I thought about getting out of town a lot. And then in grade school, my two best friends were from China. I would look at the characters they were writing and was always interested in this secret code language they seemed to have. So when I grew up and decided to go to the University of Wisconsin-Madison, I quickly realized I wanted to do something [international]. But at that point I was still interested in foreign affairs, or maybe working for the state department. Japan was the big growing business force in the world at that time, so I thought maybe it would be a good skill to learn a foreign language, and going back to those grade school friends I had, I decided to learn not Chinese but Japanese. I ended up majoring in Japanese and it just so happened that the University of Wisconsin started up a Japanese exchange program at the time, and they needed two students to spend their junior year over at a Japanese university, and then two Japanese students would come over to Wisconsin. I was chosen to go over there and do this great program. I stayed with a Japanese family in my junior year. It was just amazing, one of the best things I’ve ever done, just to have the opportunity to immerse yourself in a foreign culture. And at that point, I was still thinking foreign service, or foreign affairs, diplomacy, maybe international business. I wasn’t too sure. But then I traveled around Southeast Asia.

Q. What happened then?
A. As I was going around places like Vietnam, Malaysia, Thailand and some of the poorer parts of the world, I saw a lot of people who were living in really impoverished conditions. You could get the sense that there was a lot of disease and so then I became interested in the idea that infectious disease was a really big problem. I started thinking maybe I should be planning on doing something medical. I tried really quickly to get all of my pre-med stuff out of the way, I took the MCATs, and then took a year off. I lived in Washington, still furthering the idea that I might work in diplomacy. I worked in a senator’s office. But then I applied and got in to medical school at the University of Minnesota. But then all throughout my career, all my personal statements about why I wanted to be a doctor, they always tended toward this trip to Southeast Asia.

Q. How did you end up at Penn?
A. I matched at Penn for international medicine residency training. I did three years here and then did an infection disease fellowship here too. I remember sitting on the oncology board over at HUP with Dr. Harvey Friedman, who started the whole Botswana program, and it was around 7 o’clock. It was late, we were tired from the day, and we started talking about what my plans were. This was just around the time that somebody from Merck had called him to see if he was interested in sending some doctors over to Botswana. Harvey said to me, ‘Hey, Greg, why don’t you go into HIV—and why not go to Botswana?’ Harvey can be a fairly convincing guy, and so sure enough, I decided I would go over to Botswana.

Q. How many times now have you been to Botswana?
A. It’s been nine trips. But when I first got there, there was basically very little in terms of infrastructure to do research. I think my first trip was in 2003 and the first thing I wanted to do was just meet the people there and see what was going on. ... And I remember sitting down with [the doctors] there and having to deal with this question they seemed to be asking, even though they weren’t overtly asking it. The sense I got was, ‘Oh, you’re another researcher. What can you add?’

Q. How did you get past that?
A. I wanted to see where they felt there was some unmet research needs. I saw Botswana as an opportunity. I wanted to do concrete research that addressed their needs and could improve the care they were delivering as quickly as possible. I wanted to have a strong local relevance while also being relevant to the broader epidemiological question globally.

Q. How did you go about doing that?
A. One of the things that was interesting to me was that there was a feeling when I first went to Botswana among the local providers that there wasn’t really a clear idea of how well the program was working. So I focused on that pretty quickly, like on the first trip I went there. I realized what they wanted was to have some data on the outcomes of the treatment programs. Really, that project was about starting to look at how these patients with very advanced AIDS and HIV infection were living after they started antiretroviral therapy. I think the reality is, when you’re in a busy clinic and treating 50 patients a day, you don’t necessary have the chance to think about and succinctly describe what’s going on in your clinic. How do you keep track of these patients when there are 50 more the next day, and the next day after that?

Q. What did your research reveal?
A. Global scale-up of antiretroviral therapy is very focused on counting the number of individuals who are starting treatment. What we’re trying to do is make a very complicated disease manageable in places where you have very few resources. But this is clearly a very complicated disease. Just starting HIV therapy is only the beginning. This disease requires life-long treatment. It’s expensive. There are high complication rates. So when I started to talk with people there, I was telling them, while initiation of treatment is important, it was also important to find out what was happening to people after they started treatment. The story of my first study there could be said to be that while outcomes in global antiretroviral therapy could be thought of as doing quite well, not every patient was being traced. And when you did trace every patient, you found a lot of deaths. The patients who were dying soon after therapy began were the sickest patients—the ones with very low CD4 counts. The reason they were dying was not entirely clear [because therapy should be effective even in sick patients] but what it revealed was a tremendous opportunity. So my research now is focused on finding what is happening to those patients who aren’t doing well. And if you can improve that, you will improve the outcomes of scale-up worldwide.

Q. You then did a second study that has also received a lot of attention, correct? What was that study about?
A. The two studies are somewhat related, in that they’re both interested in this idea that, although initiation of therapy is important, it’s not the whole story. Monitoring patients and improving outcomes is really where the future of global scale-up is. The traditional method for [tracking patients] is looking at CD4 counts, but now we have a line of research that I have developed along with Robert Gross, a collaborator of mine here, who developed a method to track patients’ adherence to therapy by measuring their pharmacy refill data. CD4 tracking is a blood-based test, a test that is really ingrained in HIV care. But there are a lot of variables in CD4 counts from day to day. That started to make us concerned that CD4 counts weren’t necessarily the most accurate way to follow patients. Another thing is that doing these CD4 tests requires a lot of resources. But a potentially much simpler way, given that every clinic distributing therapy has access to records that tell them when patients came back for their meds, was to track pharmacy refill adherence. And we revealed that following adherence patterns worked as well or even better than following CD4 counts. This is potentially a new paradigm … in order to help doctors predict how well a patient is going to do and also potentially intervene before bad things happen.

Q. This has to be an incredibly gratifying line of work.
A. Yes, it is gratifying. But if there’s one thing I miss it would be direct patient involvement. This is an all-consuming line of work. Grant funding is difficult to get now, and in order to succeed in this career you have to be very driven and spend a lot of time writing grants. That means less time treating patients. But it’s gratifying when you see work do something, when it appears to have an effect. I think the paper I did with Robert Gross could potentially be incorporated into [global] guidelines. And I don’t know that for sure, but I have heard people talking about it.

Q. Do you feel the situation in Botswana can improve?
A. Botswana is really a model country in figuring out how to deal with HIV. So I’m very optimistic about how things can go there. They’ve addressed HIV on almost every front. You see billboards about HIV there, much more than you do here. They’ve rolled out universal testing, so if you come in to get medical care, they’ll tell you, ‘OK, you’re sick, I’m going to take care of you, but I’m also going to test you for HIV.’ They’ve rolled out free drugs to all citizens who have AIDS and who quality for treatment. They’ve achieved nearly 90 percent coverage for therapy of those who need it, and so I’m very optimistic. They’ve made incredible progress.

Originally published Oct. 30, 2008