Nearly three decades have passed since the discovery of HIV, and James A. Hoxie, director of the Penn Center for AIDS Research (Penn CFAR), has been involved with the epidemic from the beginning.

When the virus first arrived in Philadelphia, Hoxie was a hematology-oncology fellow in the Department of Medicine studying basic questions about the CD4 cell, which just so happens to be the immune system cell that is destroyed by HIV.

For the first few years of the epidemic, HIV was only defined, laboratory wise, by the absence of very low levels of CD4 cells. As the years went on, Hoxie remembers people coming to him to learn their CD4 cell count.

“I was still in the early stages of my career forming, and this was an incredibly important and interesting and challenging problem that was unfolding,” he says.

Things have changed a lot in the years since. While still a dangerous, incurable disease, HIV no longer means certain death. New medicines and therapies have enabled many of those living with the virus to suppress it to undetectable or barely detectable levels.

“What’s happening now is incredible compared to what was happening before there were effective treatments,” Hoxie says. “It wasn’t until we had the protease inhibitors with HIV [in the mid-1990s] that we began to be able to use drugs in combinations, and that’s where the breakthroughs happened. Short of that, people were just dying.”

At the Penn CFAR, one of only 20 National Institutes of Health-funded Centers for AIDS Research in the United States, Hoxie and his staff work with HIV/AIDS investigators at the Children's Hospital of Philadelphia and The Wistar Institute to foster basic, clinical, social and integrated HIV/AIDS research on campus and coordinate efforts to develop campus resources that would be of general use to AIDS researchers.

The Current recently sat down with Hoxie (pictured above with lab assistants Andrea Jordan, right, and Beth Haggarty) to discuss his nearly 30 years in HIV/AIDS research and his thoughts on a possible cure.

Q. When you first encountered HIV/AIDS, were you able to see its potential to balloon into a worldwide epidemic?
A. The first description that was later recognized as really being HIV was in 1983. So the clinical side of the epidemic was first reported in 1981. In 1983, we had this first look at what this was but nobody really knew what to make of it. And it wasn’t until about a year later in 1984 that everything came together with a series of papers. By that time, we had many people who were dying of AIDS throughout the world and it was well appreciated that whatever was causing this, that this epidemic was a catastrophe.

Q. Where are we today in the fight against HIV/AIDS? Would you say we are making progress?
A. We have a profound understanding of how the virus works. There have been many new areas and insights into viruses in general as a result of studying HIV, so our basic understanding of what this virus is, how it works, why it’s so crafty, that’s been a success story. There’s no question that tremendous breakthroughs have come as a result of studying HIV. There are many things that we don’t know about it but I think we are very good now at asking the right questions. Basic science has flourished in coming to grips with HIV. In terms of therapeutics, that’s another success story, clearly. Although in the early days one drug at a time was never enough—because HIV will always get resistant to one drug—when more kinds of drugs became available, [things greatly improved]. And they didn’t just become available, they were developed because of targeted, rational approaches that build on the basic knowledge of HIV. So first you understand what you’re dealing with and then you come up with rational, targeted ways to attack it and the drug companies did exactly that and then came up with different kinds of drugs. When those drugs began to be used in different combinations, attacking the virus in different ways, that’s when the HAART era was upon us—Highly Active Antiretroviral Therapy—and the benefits of that were immediately seen. Death rates began to go down in the U.S. So we have many drugs; we continue to find new drugs. Every new drug is another weapon. That said, there are still viruses that can get resistant to even combinations of drugs and there are many parts of the world where people don’t have access to the drugs.

Q. Do you believe there will be a cure for HIV in your lifetime?
A. HIV is a retrovirus. In the lifecycle of the virus, it gets into a cell, takes the cell over to make more viruses, and that infected cell now produces more viruses that go on and do the same thing. One of the steps between the virus going in and the new viruses coming out is that the virus becomes part of the chromosomes of the cell. To take over a cell means that virus’s genetic information becomes part of the cell’s genetic information. When you ask, ‘How do we cure HIV?’ you’re saying, ‘How do we carve out the genetic information of HIV that’s in the genes of the hosts?’ And we don’t really know how to do that. We don’t have drugs that can be given now that have that ability. So I think in the way we think about drugs and the way we understand the viral life cycle, there aren’t things on the drawing board today that tell us how to do this. But anyone who’s been in science a long time knows that many things have been thought of as not being possible based on the information we have now and yet in time, with new understandings of biology, perhaps even new drugs, new things can be realized.
I don’t want to say that a cure is never going to be possible but I think that at least based on what we know now, there isn’t a clear strategy for carving the HIV gene out of the genes of the host. We just don’t have a technology that can do that today. It is important for people to realize in an era where individuals are now living with HIV, as a result of the drugs, and they’re living longer, we don’t really know what the upper limit is. People may well have a length of life that’s comparable to somebody without HIV. We have to wait and see as people get older and older, and they are, thankfully. But that perception that we have of people growing older with HIV while they’re taking their drugs, that sort of belies the fact that to be infected with HIV is to be infected for life and to take these drugs to control HIV means that you need to take those drugs for the rest of your life. So infection by HIV is never to be taken lightly.

Q. There has been controversy surrounding the use of abstinence-only education in preventing HIV. Do you support it or do you think there are more effective methods?
A. Abstinence should be encouraged but, in fact, as the only way to deal with prevention, I don’t believe it will work. I think the reality is that people have to have other options. Condom use, the lack of sharing of needles, all these kinds of practices are just as important to get across. I think there’s been a lot of controversy with the [Bush Administration’s] view of abstinence. In some settings, they have taken the view that what abstinence-only means is that you really won’t embrace the role of condoms in dealing with the epidemic. Condoms prevent HIV so how can you not advocate informed and appropriate condom use in populations? There’s not one prevention message for everybody and that’s where you get into some frictions because the people who are saying abstinence-only are saying that if everybody is abstinent, you wouldn’t have an AIDS problem. The reality is that people need different options. Abstinence works, condoms work, and anything that works needs to be embraced and supported.

Q. A lot of people are still uneducated about the disease. One study found that some Florida teens think drinking bleach will prevent HIV. Why do you think people are still so uneducated about the virus?
A. Well, how are they hearing? They’re not hearing in the right ways so they’re not educated. Now we ask, ‘Why has education failed?’ You have to go to the schools, you have to go to the families, you have to go to the churches and ask where can education be improved. It’s horrible when you hear about things like this but it’s a failure of education. If there’s ignorance, people will fill in that gap with all sorts of beliefs, and that’s true of people and that’s not just limited to AIDS. The bottom line is that education is a weapon to fight HIV but education is not limited to one place. AIDS cannot be neglected. I just returned from Africa where a university in Botswana, in fact the only university in Botswana, has made the decision that they are creating a center to deal with the educational aspects of AIDS. It was very touching when I was talking to an individual there about the rationale for creating this center. Her reason for why this was such an important thing to have in Botswana—where large numbers of people are infected with HIV—was ‘HIV touches everything,’ that it doesn’t matter whether you’re studying mathematics or physical education or business, AIDS touches everything. There was going to be something taught about AIDS in every course in the university. That’s just an extreme example but in fact, it’s right on.

Q. Former President George W. Bush is given much praise for attacking AIDS in Africa. Do you think we are doing enough domestically to fight AIDS?
A. We are still fragmented in our approach to prevention. There’s not really a consistent theme. And the support for preventive efforts is still lacking so there needs to be a more focused and aggressive approach to prevention efforts, and this is outside the context of the vaccine science. So the hardest to reach, hardest to hit populations are still neglected. We need aggressive leadership that is going to focus on the ongoing problem of the AIDS epidemic in the U.S. It has not gone away.

Q. Is there enough AIDS funding for scientists and specialists to do the work that needs to be done?
A. In the last five or six years, the NIH budget has been flat. ... There is really a crisis in funding research. Roughly one in nine grants are getting funding right now and that’s a disaster. It drives people away from careers in science because they take one look at what established people are having to do just to keep their labs going and they’re saying forget it. Is there enough money? No. What do we need money for? It’s very clear, especially from recent failures of certain vaccines, that we need more basic research. And unfortunately, it is basic research that has suffered as a result of the funding crisis. In a nutshell, we need more money. And it isn’t just AIDS, it’s the NIH budget in general that has suffered across the board in the last five or six years to the extent that people are being driven away from working in science. So that is a huge, huge problem.

Q. What goals do you have for the Penn Center for AIDS Research?
A. The goal of these centers is to make sure that scientists on our campuses are working together and different kinds of scientists come together to address new and creative kinds of approaches. Getting behavioral scientists to work with basic scientists, getting clinicians to work with vaccine scientists, to get people who work in the U.S. to work with people who work in Botswana. It’s called interdisciplinary research and so CFAR is really about trying to breed that spirit where you have a collegiality of people working together. We all try to do that and I think that our hopes are that, depending on the individuals that you are bringing together, that you’re going to come up with breakthrough discoveries. That’s what every center like this wants to be able to do. At Penn, it’s not just the medical school, it’s the entire campus. We have an enormous range of talent to draw from.
Our goals are really to make breakthroughs, to create an environment that is exciting for students, to make them aware of the challenges and the opportunities for establishing careers in AIDS research. If they’re not going to become specialists in AIDS, we want them to at least understand the importance of the problem and the bottom-line messages of what people in the world need to understand about this ongoing epidemic. Another huge aspect about the center is that we maintain strong alliances with our community. The Penn CFAR has a very strong and proactive community advisory board. We benefit by advice that we get as to what are important themes in the community that we need to pay attention to and we have regular meetings with them. We are always in a process of becoming. We want to be better than we were. What we were five years ago isn’t good enough now because things change, the science changes, needs in the community change. Our goals are really to stay on the cutting edge, bring people together, stay in touch with our community, stay in touch with our campus and inspire.

Originally published Feb. 5, 2009