- Home>
- Specialties>
- HIV/AIDS>
- Feature
Surviving AIDS, and Beyond
An Interview with Dr. Robert Zackin, an HIV researcher and the first HIV-infected individual to receive a heart transplant.
In February 2001, Dr. Robert Zackin became the first HIV-infected individual to receive a heart transplant. A biostatistician whose research focus is HIV, Dr. Zackin was the senior author of the paper published in the New England Journal of Medicine summarizing his case and providing 2-year follow-up from his successful transplant (N Engl J Med 2003;348:2323-8). Recently, Dr. Deborah J. Cotton spoke with Dr. Zackin about life as both patient and researcher, the controversies surrounding solid-organ transplantation in HIV-infected individuals, and surviving AIDS and advanced cardiomyopathy.
Dr. Cotton: When I first met you in 1993, you were finishing up your degree and were quite sick with AIDS, but when you started out on the path to becoming an HIV researcher, you didn't know that you were HIV-infected. What drew you to HIV research?
Dr. Zackin: To be honest, I didn't really seek out a life in HIV/AIDS research. To the best of my knowledge, I was infected sometime early in 1986. I was in between college and graduate school. I can't say that I was drawn to HIV research by any great concern about my own risks for HIV, nor because any friends of mine were infected (it was still early in the epidemic), nor for any overarching concerns about the gay community. I was trying to figure out what I wanted to do with my life, and I started working for a small pharmaceutical company doing HIV research. I was certainly attracted to the work because I knew it was important and could save lives, but I had very little personal investment in it.
Dr. Cotton: Back in 1986, were you worried about getting AIDS or was it not even on your radar screen?
Dr. Zackin: It wasn't on my radar screen at all. I decided to go to graduate school, enrolled at Harvard, and continued down the path of HIV research, feeling that it was important and interesting, but I still didn't feel that I had a personal stake in the work I was pursuing. However, between 1986 and when I started Harvard, I did have suspicions that I might be infected. My overall health was great, but there were minor symptoms that I noticed.
Dr. Cotton: Were you frantic or calm about not knowing? Did you consider getting tested?
Dr. Zackin: I'd like to think that I was perfectly calm. I was in my 20s and in denial. I never seriously considered getting tested because, at the time, there wasn't much I could do if the result was positive. Then, at the end of '91, I had what I thought might be HIV-related pneumonia. Still, I put off getting tested until the twelfth hour. In March, immediately after my orals, I went away for the weekend. I became very ill and returned to Boston and went straight into the hospital with pneumonia. That is when I tested positive for HIV. I had PCP and a CD4 count of 20 cells/mm3.
Dr. Cotton: In the end, was the diagnosis a shock to you or did it feel like something you'd expected?
Dr. Zackin: It was and it wasn't a shock at the same time. I tried to accept the diagnosis and incorporate HIV into my life pretty quickly. I think that accepting situations and asking myself, "what are you going to do about it, now?" is in my nature, and can be quite beneficial under circumstances like these.
Dr. Cotton: Keeping optimistic must have been very difficult given how bleak the outlook was at the time. As an AIDS doctor I, recall the years from '92 to '94 as being the most depressing period in the epidemic as we watched the number of AIDS cases soar and our available drugs failed to significantly alter the course of the disease. How did you cope during those years?
Dr. Zackin: I decided that I was going to try to survive. The first few years stank. I was on a clinical rollercoaster. I'd develop a complication or an opportunistic disease, and it would be really horrible for a while, and then I'd somehow get back to baseline. I developed Kaposi sarcoma in October '92, then disseminated Mycobacterium avium complex and gastrointestinal cytomegalovirus in '93 and '94. Later in '94 I developed pulmonary KS.
Dr. Cotton: Were you open about the diagnosis at the time?
Dr. Zackin: I took a few weeks off while recovering from the pneumonia. Then before I went back to work I sat people down one-by-one and told them that I was HIV-positive. Most people were pretty supportive in the sense that they weren't going to let this color our relationship. Having HIV was never something I was ashamed of.
Dr. Cotton: As a statistician at Harvard, you were surrounded by HIV researchers, but they weren't necessarily medical experts, and they weren't caring for HIV-infected patients. Did they treat you differently? What was this like for this group of HIV researchers to suddenly have someone with their disease among them?
Dr. Zackin: One or two people treated me differently. It bothered me to be singled out, but it bothered some of my colleagues even more. Most people were tremendously supportive and respectful. I was able to help to explain clinical phenomena to colleagues. However, there were some aspects of the disease that I kept to myself.
Dr. Cotton: So, how did you survive? What were the first steps you took?
Dr. Zackin: I started on antiretroviral therapy almost immediately. First AZT monotherapy and then dual-NRTI therapy with AZT, 3TC, and d4T in different combinations. However, I remained quite sick, with my CD4-cell count reaching zero. When my doctors discovered pulmonary KS, I received liposomal daunorubicin, to which I had an excellent response. When you first met me, my weight was considerably less than what it should be. However, I was lucky. I enrolled in one of the first protease-inhibitor trials, and I received ritonavir, which I've taken ever since. That was certainly the turning point in my HIV disease.
Dr. Cotton: But your KS therapy came with a price.
Dr. Zackin: Yes, we opted for pretty aggressive chemo, which I don't regret -- I might not have survived otherwise. However, in late '95, I developed shortness of breath, and tests revealed that I had cardiomyopathy. I went off of the liposomal daunorubicin and switched to paclitaxel, which I continued into '96. My cardiomyopathy continued to progress, and in late '99 I began to receive continuous dobutamine.
Dr. Cotton: How did you become a transplant candidate? How much resistance did you face given your HIV status?
Dr. Zackin: By the time I received the transplant, I was in dire straits. I was placed on an intraaortic balloon pump while waiting for a heart. However, I'd started to look into the matter before that as my condition worsened. At first, I was convinced that I would not be eligible because of my HIV status. A lot of transplant centers wouldn't even let me in the door. I tried not to let myself become discouraged, and it helped that attitudes towards HIV disease in general and transplants in particular seemed to be shifting as patients were living longer, healthier lives. At some transplant centers, the cardiologists were willing to evaluate me, and they were in favor of giving me a transplant, but the boards that had the ultimate authority decided against it. Then in October 2000, I learned that the Cleveland Clinic was willing to actively consider HIV-infected transplant candidates. It helped that my situation was critical at the time, that the cardiomyopathy was believed to be due to the daunorubicin treatment, and that my response to antiretroviral therapy had been quite good, once I'd achieved an undetectable viral load and a solid increase in CD4-cell count. I traveled to Cleveland in January 2001, they decided that I was a good candidate, and I was fortunate that a heart became available within the month. I was also lucky to have insurance that covered the procedure.
Dr. Cotton: Do you remember what you were thinking when you found out that a heart was available and prepared for the surgery?
Dr. Zackin: I don't remember much. After a lot of work to get myself on the list, it was odd to have so little to do once the time came for the procedure.
Dr. Cotton: How soon afterward did you know that the transplant had been successful?
Dr. Zackin: The risks, of course, are ongoing, but the improvement was immediate.
Dr. Cotton: One of the concerns with solid-organ transplantation in HIV-infected individuals is that the immunosuppressive drugs required to protect against rejection could spur progression to AIDS. How was this managed in your case?
Dr. Zackin: In my case, it was made even more complicated because I was taking ritonavir, which has pharmacokinetic properties that prolong the half-life of cyclosporine. We opted to continue the ritonavir, because it had been so successful for me. So it took quite a lot of work to figure out how to adjust the cyclosporine dosage. The bottom line, however, is that I've experienced no HIV progression and my viral load remains undetectable, despite the fact that my CD4 count has dipped below 100 cells/mm3 at times.
Dr. Cotton: But it hasn't been all smooth sailing.
Dr. Zackin: No. I've had several episodes of rejection and other complications, such as gouty arthritis and anemia. I now have to receive transfusions every two or three weeks. However, I feel fine, have returned to work, workout at the gym daily, and am living a full life. I'm treating my HIV much as I have for years. Much of the time, the scar is the biggest sign of the transplant.
Dr. Cotton: Although you started out as an HIV researcher for reasons that weren't personal, the case history that was published in the New England Journal of Medicine must have felt different, as you were both the patient and one of the authors.
Dr. Zackin: Certainly, in this instance it was quite personal. However, I still maintain that my work and my personal life are separate. My research may go in very different directions in the future, and my focus may even move away from HIV.
Dr. Cotton: There are both medical and ethical concerns about solid-organ transplantation in HIV-infected individuals. What do you now make of these concerns? What does your experience tell us about them?
Dr. Zackin: On the medical side, the key issues are immune suppression and drug interactions. On the ethical or political side, the issue is framed in terms of the limited number of organs available and the difficulty in determining who should receive them. My case shows that the immunosuppression following transplant doesn't necessarily cause disease progression and that the drug interactions can be managed. Obviously, mine is just one instance, but there are ongoing studies in liver recipients and kidney recipients to help clarify these issues, and there's been at least one more heart transplant in an HIV-infected patient since my surgery.
The ethical issues can be difficult to grapple with, but from one perspective, if HIV-infected patients aren't at particular risk from transplantation or if that risk can be effectively managed, then there is no cause to hold their serostatus against them when evaluating their candidacy for transplant.
— Robert Zackin, ScD, and Deborah J. Cotton, MD, MPH
Dr. Zackin is a biostatistician at Harvard University. Dr. Cotton is a Past Editor-in-Chief of AIDS Clinical Care; Chief, Medical Service at VA Boston Medical System; and Professor of Medicine at Boston University Medical School.
Published in AIDS Clinical Care December 1, 2003