AIDS Therapy in the New Millennium

Medically Reviewed by Jacqueline Brooks, MBBCH, MRCPsych
From the WebMD Archives

Feb. 1, 2001 -- Two things are being left behind as AIDS therapy marches into the new millennium. Gone -- for those with access to anti-HIV drugs -- is the despair of the days when AIDS meant death. Gone, too, is the fervent hope that drugs can cure HIV infection.

"There is no way this phase of the AIDS epidemic -- in the U.S. -- will be anything like the first phase of the epidemic -- it will be a fraction of what we saw then," leading AIDS researcher John W. Mellors, MD, tells WebMD. "Some people are going to do great, but some are going to slip through our hands. It is going to be this way for a long time. We will edge up, then fall behind."

It seems like only yesterday -- actually it was the mid-1990s -- when the advent of potent triple HIV therapy held out the promise that HIV could be cured. Researchers calculated that only a few years of highly active antiretroviral therapy (HAART) could wipe out the AIDS virus. They were wrong.

Only two years ago, many of his peers thought University of California at San Francisco researcher Jay Levy had flipped his lid when he publicly rejected the cure-oriented "hit hard, hit early" approach to AIDS therapy. Now the same scaled-back approach he advocated then will soon be enshrined in official AIDS therapy guidelines. These new guidelines will reflect a more sober mood among doctors whose goal now is to extend the benefits of therapy -- and to minimize its toxic side effects -- for as long as possible. They advise holding off taking AIDS drugs until blood tests show that a person's immune system is beginning to fail.

"The new era we are in is 'hit early is wrong' -- that approach was not based on the understanding you would have to treat people for so long," Levy tells WebMD. "It is a matter of time before the drugs no longer work. That is what we are learning. If you start too early, your options are used up. It is predictable. Drugs are running out, and we don't have anything great on the horizon."

Levy -- one of the first researchers to isolate the virus that causes AIDS -- thinks future guidelines will go even further, holding off treatment until the immune system is on the verge of collapse or until AIDS symptoms begin to appear. "Now we are saying let's wait until a person develops symptoms and the drugs really will help," he says.

And it's not just a matter of side effects. If a person takes AIDS drugs long enough, drug-resistant strains of HIV eventually will appear. This means switching drugs again and again until there aren't any more drugs left to take. Many patients already have reached this stage.

"This is a heartbreaking group to deal with," says Mellors, chief of the division of infectious diseases at the University of Pittsburgh School of Medicine. "What will be required for them is access to multiple [experimental drugs]. ... But we have a significant waiting time for a lot of people. I have people I would love to put on these drugs right now, but they have to wait."

Atlanta AIDS clinician Kimball Johnson, MD, has been treating patients since the early days of the epidemic. She agrees with Mellors that the bad old days are gone -- but that some patients are at the end of their ropes.

"I started my AIDS practice with 14 people in the hospital at a time," Johnson tells WebMD. "This past year, I saw only one death, although last year I had some patients who had been around since the beginning of the epidemic who had run through all of their options. They began single-drug therapy with AZT, and then sort of had serial monogamy with one drug after another until they got resistant to every single drug. Those are the ones we are seeing funerals with."

Mellors says it isn't simply a matter of who began with single-drug therapy -- what counts is whether anti-HIV drugs can suppress the AIDS virus.

"Some patients who went on monotherapy and switched to triple therapy are fine, and some who started with triple therapy are having some problems," he says. "In our clinic, 60% of patients do well -- they have undetectable virus. About 40% of these patients who have been put on anti-HIV drugs have delayed toxicities that result in changes in their bodies -- wasting of the face and limbs and central accumulation of fat -- and additional longer-term toxicities that include bone loss and increased risk of [heart] disease. But in terms of their HIV infection, they are doing well: Their virus is suppressed, and they have recovery of immune function."

Recovery of immune function is the key to the future of AIDS therapy. Most patients who receive anti-HIV drugs regain strong immune responses -- but for reasons that remain unknown, these immune responses do not work against HIV itself.

"What you have to do is boost the immune system -- that is really the secret to controlling this virus," Levy says. "You might do it by immunization, but we don't have a good vaccine. Or the more recent emphasis is going to be on structured treatment interruptions, where you stop the drugs for a while, let the virus come back up so the immune system can get a look at it, and then restart the drugs again. And [the immune-boosting substance known as] IL-2 has regained popularity." He explains that IL-2, when given with HAART, increases infection fighting cells, but unfortunately, they don't target the HIV. "Now the question is how to program those returning cells to fight HIV," he says

These medical questions are not the only clouds looming on the HIV horizon. Atlanta's Johnson says that for the first time in a long time, she is seeing a steady increase in people newly infected with the AIDS virus.

"It is alarming that we are seeing a resurgence of new HIV diagnoses," Johnson says.

Mellors predicts that he will see the same thing. "We are seeing a resurgence of HIV risk behaviors so it is only a matter of time," he says. "I don't want to sound pessimistic, but it is almost predictable that we have great resources and motivation as human beings for only a short period of time. It's our attention span. This is the same thing that occurred with tuberculosis -- absolutely the same thing. It will be two steps forward and one step back -- that is the story in most infectious diseases. For global control of AIDS, we are really talking about the need for an effective vaccine. This is not to say that for individuals the drugs can't have great benefit -- but for the disease as a whole, it will be to and fro for a long time to come."

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