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AIDS Therapy in the New Millennium

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"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

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