AIDS Research Past and Future
An Interview with Jeffrey Laurence, M.D.
Dr. Jeffrey Laurence has been associated with the American Foundation for AIDS Research since its inception and became amfAR's Senior Scientific Consultant for Programs in 1992. He is Professor of Medicine and Director of the Laboratory for AIDS Virus Research at Cornell University's Weill Medical College, as well as Associate Attending Physician at New York-Presbyterian Hospital. Dr. Laurence's career as a physician and research scientist spans the history of the AIDS epidemic.
In this interview (conducted in December 2000), he discusses his early career and the challenges HIV/AIDS researchers face today.
|Dr. Laurence in his lab at Cornell University's Weill Medical College|
amfAR: How did you first get involved in AIDS research?
Laurence: In 1979, I went over to Rockefeller University to do research and start working with children with immune deficiencies and people with leprosy. In studying the T-cells and the immune cells of these leprosy patients and immune-deficient children, I would go over to the hospital and look for people who did not have obvious diseases or obvious immune system problems -- people who "normally" had an unusual infection. It was then that I started seeing these young men with unusual pneumonias. In 1981, our hospital, along with Mt. Sinai and the University of California in San Francisco, were the first three institutions to describe AIDS in a single issue of the New England Journal of Medicine.
amfAR: So you were in this from the very beginning?
Laurence: Yes, I noticed the same things that Dr. Mathilde Krim and Dr. Joseph Sonnabend were noticing [at New York's Memorial Sloan-Kettering Cancer Center].
amfAR: Did you know them at that time? Share information with them?
Laurence: Not in 1981. I met Dr. Krim later, when she called me and asked if I would join the Scientific Advisory Committee of a new foundation that she was starting with Elizabeth Taylor.
amfAR: So you had an early reputation for expertise in the science of HIV/AIDS?
Laurence: I was someone who learned a great deal about AIDS early on in the epidemic. I had the great good fortune in November of 1982 to meet Luc Montagnier, whom few people had ever heard of. He came to Rockefeller to talk about a new virus he had discovered. I had almost 100 patients at that time that had these unusual diseases, mostly young gay men, and Dr. Montagnier invited me to go to Paris with him.
I went to the Pasteur Institute at the end of 1982 and brought back with me one of the very first samples of his virus. Actually, it was before anyone in the United States, as far as I know, had it. Dr. Montagnier and I published a paper together in the New England Journal of Medicine in 1984, in the same issue that Dr. Robert Gallo published his paper. He described HTLV-III as the cause of AIDS and we described LAV as the cause of AIDS. Of course it was the same virus.
amfAR: What has been your biggest frustration regarding AIDS and the response of the scientific and medical community?
Laurence: I'm much less frustrated now than I was in the beginning. In the beginning, it was a constant question in my mind: "Why isn't every virologist and every hematologist and every infectious disease expert stopping whatever they are doing and working on this disease?" I couldn't understand why people didn't see the importance of this epidemic.
I remember it started very early on when my director at Rockefeller felt we should get in and get out. It was going to be a very short-term issue, the virus would be discovered, there would be a treatment, and it would go away. And that couldn't have been more wrong. But I think that [his] impression was shared by a lot of people in the medical community, and so they didn't stop what they were working on to devote their attention to this new disease.
And there are always issues of discrimination and fear. The fear of contagion was a very big deal way back when. One person would take my suit jacket and put it out in the hall. The mailman wouldn't bring the mail up to the third floor. Everyone was scared -- really, really scared. After all, it was a new virus, and people didn't know much. You'd go to a party and people would ask what work you did, then they would slowly move away from you and start eyeing the punch bowl. I asked one of the chief doctors at Rockefeller very early on why he wasn't supporting AIDS research. He turned to me and replied, "Let's just say it's a very unattractive disease."
amfAR: And today?
Laurence: Today, of course, it is very different. There are still problems with the way the grants are distributed federally and with the slowness of the vaccine effort, but the federal government has allocated over $2 billion annually to AIDS treatment and research. That's a good chunk of money. I would argue that if we had had anywhere near [that] amount of money ten years ago, we would have made amazing strides by now. But at least now everyone is paying attention.
Also, people have bought into the idea that by attacking the problems associated with a disease that has a known cause, and by looking at some of its complications -- everything from stroke and heart disease to blood clotting problems to kidney disease to cancer and so forth -- that we are going to learn how to treat those diseases in the absence of HIV. (See amfAR's publication "Broad Benefits of AIDS Research.")
amfAR: What are the biggest challenges we face in dealing with the epidemic today?
Laurence: Prevention is the major challenge. No viral epidemic has ever been cured by treatment. They've only been cured by prevention, and the best kind of prevention is a vaccine. Most people, including myself, believe that we will not have a vaccine in our lifetimes -- that is, a sterilizing vaccine, like a polio vaccine or a flu vaccine, that prevents the majority of people from getting infected. The kind of vaccine that is going to prevent everyone from getting this disease, the kind we really need, is a very, very long way off. Given our current technology, what I believe we will have within this decade is a partially protective vaccine -- one that might prevent, say, one in 10 people from becoming infected. This would still be a huge benefit to countries with very high rates of HIV transmission, though. And one can never underestimate the possibility of a new breakthrough in vaccine research that would temper my pessimism.
The amount of money that we are putting into prevention, apart from a vaccine, is very low, considering the need (it's $400 million now). The federal Centers for Disease Control and Prevention (CDC) have acknowledged recently that they need to do much better in terms of prevention strategies. In terms of new HIV infections in just the United States, there were 40,000 infections in 1991, there were 40,000 infections in 1992, 40,000 infections in 1995, and 40,000 infections in 1999. It hasn't changed one iota. The kinds of people getting HIV is what has changed. A recent report from the Institute of Medicine (IOM) commissioned by the CDC underscored the need to rethink our strategies. (See the IOM's report, "No Time To Lose: Getting More from HIV Prevention.")
|Members of amfAR's Scientific Advisory Committee (SAC) review grant proposals|
amfAR: Why do you feel the peer review process (as conducted by amfAR's Scientific Advisory Committee) is important in awarding grant money?
Laurence: I sit on grant review panels for the [the National Institutes of Health] and also for amfAR. The federal government, per grant, gives out a lot more money than amfAR does, but they are much more "risk-averse." amfAR, in giving smaller grants for innovative ideas, can take more of a chance. amfAR's grant review process is important to screen out the people who will get federal money anyway, or who are working with ideas that are not necessarily the most pressing things we could do today, and steers funds to promising people and ideas that other agencies are not taking a risk on.
amfAR: If an actual clinical "cure" and vaccine for AIDS, along with the logistics of using them to end the epidemic, appeared tomorrow, what new area of research would you pursue?
Laurence: If we had a vaccine at this very moment, it would still be a very long time before it was disseminated to all the people who need it. The focus of my work in the last several years has been less on therapy itself, and more on the complications faced by people living longer with HIV.
We have almost a million people living with this virus in the United States, and as they live longer, they are getting unusual health conditions. The National Heart, Lung and Blood Institute predicts that one out of every ten people dying with the AIDS virus today are dying of primary heart disease, which includes heart attacks, accelerated hardening of the arteries, or strokes. The good news is that the government just decided to put a fair amount of money forth to discover why, hoping that there may be some broad benefits to the study of this disease.
In addition, the National Cancer Institute predicts that one out of every four people with HIV today will develop cancer, and we're seeing some very peculiar kinds of cancer. Kaposi's sarcoma, something we used to see at the beginning of this epidemic that we hoped was going away, is coming back again. We are also beginning to see lung cancer, cancer of the stomach, cancer of the pancreas, and cancer of the intestines -- all in 40-year-old men, even though their viruses are controlled. Something in their immune system is not working well despite control of HIV with antiviral drugs. That's become a large part of what I do now and what we're trying to investigate.
amfAR: Can you clarify a few things that we've seen in the news of late? For example, natural immunity?
Laurence: Natural immunity is very interesting because it might help in vaccine design. For one thing, there is an almost absolute natural immunity. That is, some people are born with a mutation, inherited from both their mother and father, in one of the genes called CCR5 that's required for most AIDS viruses to infect cells. If you've got both copies of these mutated genes from your mother and your father, it is virtually impossible to become infected. Not completely impossible -- there are some strains of HIV you can get infected with -- but it is incredibly difficult to get infected. This mutation accounts for a very small percentage -- perhaps 5 percent -- of people who appear to be naturally resistant to becoming HIV infected.
There are multiple reasons why some other people seem to be naturally protected against getting the virus, and most of those natural protections are relative. An interesting one that has been studied is the case of commercial sex workers in Nairobi, where a group of about 1,800 women have been followed since the late 1980s. These are women who have between 20 and 30 HIV-positive sex partners a year and have gotten infected with the virus themselves over the years. But in this group of 1,800 women, there's a group of about 30 women who, over a decade of follow-up, have never gotten themselves infected. The biggest clue as to why they are protected came when six of these women decided, for a number of reasons, to stop commercial sex work for a period of between two and six months. All six of the women returned to their commercial sex work, and all six of them got infected with HIV.
The hypothesis of the researchers in Nairobi and their collaborators at Oxford University is that these women were possibly immunizing themselves with dead or live virus through their work. As long as they kept that immunization up they were protected, as though they were injecting themselves with a vaccine every day. When they stopped and then resumed, they no longer had this natural level of protection. It's just hypothesis, by no means proven, but at least it's given a little bit of hope to people who work on vaccines. A lot of people are doing animal experiments now to try to test some of these theories out.
amfAR: Who is the Berlin patient?
Laurence: The Berlin patient was a man who had HIV for a number of years, and who had HIV therapy. He decided, voluntarily, to stop his medications. His viral load was undetectable, with only one minor blip when he re-started his medications and then re-stopped them. For over two years of follow-up now he has had an undetectable viral load. He still has the virus -- it's at very low levels and undetectable by the standard tests for the virus in the blood -- but his T-cell counts are very good.
This led people to suggest that what we are doing wrong in HIV therapy is prescribing drugs for a long period of time and not stopping. Maybe if we performed STI (strategic treatment interruptions), which is giving the drugs for a period of time and then stopping them, some or most individuals might never have to take the drugs again. That argument was boosted by another study in which a group of about 100 HIV-infected people decided, like the Berlin patient, to stop taking their drugs. Five of those hundred never took those drugs again. They maintained good T-cell counts and undetectable viral loads without doing anything in the way of treatment.
The idea now is that there is, naturally, a small group of people who can be treated for a short period of time (perhaps a year or two) with drugs and then can get away without ever taking drugs again, perhaps five out of a hundred people. There are two large studies in the United States, and several others around the world looking at this now.
The bottom line, to my mind and to most people's minds, is that it's incredibly unlikely -- if not inconceivable -- that you can treat an individual for a short period of time, shortly after they are infected, and then they stop all of their therapy expecting to maintain an undetectable viral load and high T-cell count. So I don't recommend doing this unless you are part of a formal study. I also wouldn't recommend this unless you started your drugs relatively early on after becoming infected, because to my reading of these studies the only people who have gotten any benefit are those who began medication early on (within six months to a year-and-a-half of getting infected).
Dr. Tony Fauci [of the National Institutes of Health] gave the best assessment of STI in saying that this is perhaps a way to decrease the expense and the side effects of anti-HIV therapy. A new study takes individuals who started relatively early in their therapy, treats them with combination drugs, and when their virus is undetectable, starts "cycling" them; that is, gives them seven days of anti-virus drug, and then stops treatment for seven days, and repeats this cycle. The idea is that perhaps you can cut the expense and side effects in half by taking the drug every other week. The results are not in yet, but [we may soon] have an idea of whether this is working or not.
amfAR: As you look ahead, what do you think are the more promising areas of AIDS research?
Laurence: It's very difficult to change people's behaviors, and a vaccine is going to be a long time coming, so we need to do the next best thing. This is something I describe as a "chemical condom" or "chemical vaccine," something that can be used locally or topically. As you use spermicides to kill sperm, you would use these microbicides, as they're known, to kill viruses. Not only HIV, but also other viruses that promote susceptibility to HIV infection, like herpes viruses. And we should be able to have that in the very near future.
amfAR was one of the first organizations to start promoting and funding the microbicide concept. (See amfAR's "Microbicide Report" publication.) We hosted a symposium at Rockefeller University in October 1999 and co-sponsored the first international conference on microbicides in March 2000. We started a grants program in microbicide development [and are about to release a request-for-proposals for additional microbicide research], and the federal government has now put a fair amount of money into this as well. Microbicides will benefit people who don't have the power to say "no" to sex, who are under-served, and who can't wait for a vaccine.