Before the 1996 International AIDS Conference, in Vancouver, few outside the HIV-research community had any idea who Dr. David Ho was. But at the conference, Ho made an announcement that made him the most famous AIDS scientist in the world. He explained how, by using a “cocktail” of AZT and several new drugs called protease inhibitors in the early stages of infection, doctors could reduce HIV in the body to undetectable levels. Patients on the drugs had already made remarkable recoveries. The news was met with nearly unchecked enthusiasm. Six months later, Ho, the CEO of New York’s Aaron Diamond AIDS Research Center, was named Time‘s Man of the Year.
Four years after this combination drug therapy became available (and three years since Ho’s announcement), HIV-related deaths in the United States have dropped dramatically: The leading cause of death in 1995 for those age twenty-five to forty-four, HIV plummeted to fifth in 1997. Today, AIDS hospices across the country are actually closing down because there aren’t enough patients to fill them. But for millions of people worldwide, the situation is still desperate. The combination therapy can cost up to $60,000 a year; the vast majority of those infected with AIDS reside in Third World countries, where treatment is often unavailable; and for a growing minority, the new drugs either don’t work at all, have stopped working or have side effects that are becoming too great to bear. All of this was reported last summer at the gloomy International AIDS Conference in Geneva.
Despite the recent bad news, Ho is energetic and upbeat. He is forty-six, surprisingly young for what he’s accomplished. He looks even younger, hardly someone you’d expect to have a seventeen-year-old son who’s heading off to MIT in the fall.
After rushing across town from a four-hour seminar he was teaching at New York’s Rockefeller University, Ho is collected and utterly calm as he speaks about the horrible deaths caused by AIDS, the greatest public-health crisis of the century: Nearly 14 million people have died from AIDS worldwide; more than 30 million are infected.
Should we be optimistic that AIDS might one day be just another treatable chronic disease, like diabetes?
The numbers really tell us. In the United States and Europe, AIDS-related deaths are down by eighty percent from three or four years ago. It’s also clear that in-patient stays have dropped dramatically for people with the disease and that even hospital spending on AIDS has decreased substantially.
It’s not completely optimistic. The therapies are not helping everybody. But there will be more drugs in the future, not fewer. And some of those new drugs are going to have better profiles, fewer side effects, easier administration. Those are things that really limit the effectiveness of our therapy today: The side effects and complex regimens really decrease patient adherence, which is key to successful control of the virus.
Is a cure still considered possible?
Many groups are still going for the home run, to see if HIV infection can be cured by purging the body of the virus with a few years of combination therapy, but that goal does not seem all that achievable in the short term. I think we’re maybe a bit closer to achieving a state where the virus could be controlled by the immune system without drugs. And that, to borrow a term from cancer therapy, would be remission: You haven’t cured the cancer completely, but you’re off chemotherapy and there’s no relapse, no symptoms, nothing. And those people who have lived a long time with HIV without developing the symptoms of AIDS — long-term nonprogressors — are telling us that this is probably doable; we just need to figure out how.
You were the champion of combination therapy. Now it’s clear that the AIDS cocktail, as it has been called, isn’t the cure-all it was once hoped to be. For some, it fails to deliver, and for others, the benefits wear off after a few years.
We have to think about what’s meant by failure. In the old days, it meant that you would develop pneumonia; you’d be in the hospital; you were going to die. That’s failure. These days the definition of failure is, you have detectable virus. And that is very different. Even among combination-therapy patients in whom the virus is still detectable, the death rate is six to ten percent. And there is no question that the failure rate will go up, because people can’t stick to and tolerate these complicated regimens. Failure rates will rise, but it’s not the same type of failure that we saw back in the Eighties.
How much do you worry that the current treatment might enable HIV to evolve into a super-virus even more dangerous than the current incarnation?
This is of some concern, of course. Most treatment failures are in some way related to either the development of drug resistance or non-adherence to the drug regimen. More and more resistant viruses will emerge, as we have seen with antibiotic resistance in bacteria. However, the real question is how quickly they will come up. All indications so far are that this is happening slowly, not explosively. Thus, we should not frighten people by suggesting that the super-viruses will take over tomorrow. But we must also monitor this situation closely.
Things might be looking up for people in the U.S., but the vast majority of people with AIDS in the world do not have access to proper medication. There are entire countries crumbling under the weight of the disease. What’s on the horizon for them?
There are close to half a dozen countries where one in four individuals is infected and certainly over a dozen where one in ten of the population is infected. Making combination-therapy drugs available to that many people is not feasible. And it’s not just a question of economics — it’s also logistics. Even if companies donated the drugs, there’s no infrastructure in place that would allow them to be administered. Those who are infected in developing countries are largely doomed.
Short of drugs, what else can be done for them?
When most of us look at the big picture, we say the only effective way to deal with this epidemic is through prevention, and there are two ways to go. One is through education. The other is to come up with a vaccine. Education has been successful in some ways, but it’s limited, and behavior modification on such a huge scale is unlikely. The long-term goal has to be a vaccine, which in some ways is an admission that we have very little to do for those who are already infected. And that is quite true.
Until a vaccine is found, though, we must continue to educate and prevent where we can. And some of our interventions are very successful — at blocking mother-to-child transmission, say. That problem has almost disappeared in the U.S. and Europe through the prophylactic use of AZT and other drugs. So maybe we could get the drug companies to agree to donate drugs or to sell them at an extremely reduced rate to, say, South Africa, Uganda, Kenya, Thailand and India. And that could lower the transmission rate from thirty to forty percent down to five percent or eight percent. That would benefit a lot of kids and protect the next generation. A number of such programs are under way, and many of the pharmaceutical companies, like Glaxo [Wellcome] and Bristol-Meyers, having made their money in the United States and Europe, feel obligated to help the developing countries and are quite willing to selectively donate many of the drugs they have.
How important is the recent discovery of the origin of HIV in chimpanzees?
It’s not important in the sense that I see an immediate translation to vaccine development or to drug development. But it’s important because it shows us how new epidemics emerge. HIV jumped from another primate species into the human population, probably between four and seven decades ago. It’s clear that Ebola and HIV came out of the jungle of central-western Africa because humans started to encroach on the territory of primate populations. They harbored certain viruses, and those viruses jumped the species. Most of the time those jumps are dead ends, but some are not, as this epidemic shows. If we are to encroach in a similar way in the Amazon of South America, what are we going to encounter? Who knows? We have to do those things more cautiously.
How are countries like Ukraine, Russia and China — places that are just starting to experience the epidemic — handling it?
The new infection rates in Eastern Europe are astronomically high, particularly among drug users and prostitutes. They are experiencing what Thailand and some other places went through only a few years ago, and it’s frightening. Obviously, U.N. and WHO [World Health Organization] programs are trying to make an impact on that. I have gone to China once or twice a year every year since 1991, and I’ve seen the epidemic go from six or seven hundred infected people to what is believed to be close to half a million today. And China has had lots of data from other countries on what it should be doing. Despite that knowledge, China repeated the exact same mistakes other countries have made by only reacting to the epidemic once it was out of control. In China, AIDS was initially related to young kids using drugs. Quite often, they don’t use needles and syringes but bamboo tips. They put the drugs on the tips and just shoot it right into their veins, then share these devices. After that, of course, the virus starts to spread through sexual transmission. And now it’s disseminated throughout [the population]. Which is exactly what happened in Africa and in India.
How do you feel about the vaccine programs in trials now?
The very fact that we at Aaron Diamond are not participants in such trials would indicate to you that we think, ultimately, we need to pursue better vaccine strategies than those that are being tested right now. Sure, I would agree that we need to explore whatever vaccines are already made and put some into human testing so that we could get data that would help us shape our future program. But most of us who’ve thought a lot about vaccine development have come to the conclusion that a vaccine for HIV will not be as simple as that for polio or hepatitis B. That’s why I think the consensus in the field is that we should test the current vaccines, but they’re not the ultimate solutions.
What is the most important thing that needs to be done in terms of prevention now?
Good education and leadership from the top. You need leadership, especially when we’re talking about the global problem. To me, one of the major problems has always been that AIDS is managed at a low level and it’s not a national priority. Look at South Africa: It rejected a program, which would have cost a few million dollars, to give AZT to pregnant women and to their new-borns. And yet it went out and bought defense equipment, planes, bombs and so on, for billions. What’s killing off South Africans more? It’s not a neighbor that’s threatening to invade — it’s, in fact, a virus spreading from within. It’s killing at such a high rate that somewhere between ten and twenty-five percent of the country’s population is already doomed. That’s a huge number. You look at countries like South Africa, like India and China: AIDS is hardly spoken about, and yet it is a major killer. If a bomb goes off and kills ten people, it becomes a national emergency. Sixteen thousand people are doomed to die each day from HIV infection. If you want to put it in graphic terms, that’s a Madison Square Garden full of people dying each day. Or several hundred jumbo jets crashing every twenty-four hours. Why, when you have this situation, you don’t have greater national leadership is beyond me. I’m not aiming these remarks at leaders in China, India or Thailand. We in the U.S. went through exactly the same thing in the Eighties. Ronald Reagan hardly uttered the words AIDS or HIV throughout his administration, when the case rate went up dramatically.
Do you think we’ll be worrying about AIDS in the year 2099?
I hope not, but I really don’t know. If we really come up with a vaccine in ten years to protect the population, then we will have a chance. That would give us about ninety years to fully implement the worldwide vaccination program. Polio is nearly wiped out, and that process has taken about fifty years. Hopefully, with future medical advances, we can do better. But the key is to come up with an efficacious vaccine in the near future. If we don’t, HIV-AIDS will be with us for at least several generations.