Checking In With AIDS Researcher David Ho

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.