Newsday - November 3, 1999
Laurie Garrett, Staff Writer

Coming on the heels of other disturbing findings regarding the limits of Highly Active Antiretroviral Therapy (HAART), the study reported in today's Journal of the American Medical Association adds to a growing uneasiness about treatment of HIV infection, the cause of AIDS.

Dr. Roger Pomerantz and his colleagues at the Thomas Jefferson University in Philadelphia studied blood samples from 22 patients on the HAART drug cocktails, which are now standard anti-HIV therapy. Although 16 of the 22 patients had nasty drug side effects or secondary infections, they were considered successes because after months of HAART therapy, HIV levels remained undetectable in their blood.

But the Pomerantz group used highly sensitive technology and discovered bits of HIV genetic material in the blood of every one of those patients. And, contrary to widely held beliefs that such bits of RNA are harmless, in the laboratory, all of those HIV fragments were capable of acting as fully alive and reproducing viruses. In other words, HAART does not stop HIV replication.

"HAART is a wonderful group of drugs for a lot of patients. But it is not a cure. It simply puts people in remission," Pomerantz explained by telephone from a meeting at the Food and Drug Administration in Rockville, Md. "We sort of keep moving the goal post. We keep pushing HIV levels down, but we don't hit zero." And zero won't be hit without available drugs, Pomerantz insists.

Which explains the seemingly contradictory observations HIV doctors have made ever since HAART was introduced into widespread use in 1996. On the one hand, most patients recover from the superficial evidence of HIV disease quickly on HAART. In today's Journal of the American Medical Association, a National Institutes of Health-led research team shows that HAART patients can stop taking anti-cytomegalovirus medicines without fear of developing the blindness-inducing CMV infections of their retinas that once commonly afflicted HIV patients.

But the moment patients stop taking their HAART drugs, HIV overtakes their bodies, and CMV and other classic opportunistic infections surface. Last week, Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, reported that two of his patients who seemed to have been successfully treated with a combination of HAART and an immune-system stimulator called interleukin-2 failed when experimentally taken off their drugs. They had seemed completely free of HIV, but when HAART was stopped, viral levels swiftly rebounded.

The rebound was caused by "virus that's alive and growing all the time in the blood," Pomerantz said.

Three years ago, HIV scientists were so excited about HAART's effects that they forecast the imminent eradication of the virus from patient's bodies. Then researchers such as Dr. Robert Siliciano of the Johns Hopkins University School of Medicine in Baltimore showed that HIV could hide out in long-living cells of the immune system, lurking in a latent state for more than 60 years. This reservoir of latent infection was the focus of many experiments, including Fauci's use of interleuken-2, which was intended to push HIV out of latency and into the range of attack with HAART.

Part of the problem , argues Dr. Bruce Walker of Harvard University in a companion editorial, is that the immune system is incapable of controlling the virus. "HAART works against us in that it puts the immune system to sleep. The longer you've been on therapy, the less anti-HIV immune response you have..." he said.

Now, Siliciano said in an interview, there are "two problems: ongoing viral replication and the latent reservoirs." Walker argues that HAART patients should be getting therapeutic anti-HIV vaccines to boost their immune response.

"The drug companies need to redouble their efforts to make better drugs. We simply can't sit still where we are," NIAID's Dr. William Paul, former director of the Office of AIDS Research, insisted.

What is needed, Pomerantz said, is "a way of completely shutting off viral replication so that you can next attack the latent reservoir."

Always watch for outdated information. This article first appeared in 1999. This material is designed to support, not replace, the relationship that exists between you and your doctor.

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