Newsday - June 30, 1999
Laurie Garrett - Staff Correspondent

But a sizable percentage of HIV patients will never get close, he and other experts said. "That obviously is difficult to do given the toxicity and cost of the current therapies," said Ho, who directs the Aaron Diamond AIDS Research Center in Manhattan.

Dr. David Cooper of the University of New South Wales in Australia said that a third of HIV patients treated with Highly Active Anti-Retroviral Therapy (or HAART, a combination of three drugs targeting different aspects of the virus) fall off the treatment regimen within six months, for a variety of reasons.

"Evidence must prevail over optimism," Cooper said, warning his colleagues that HAART, as currently executed, is not the answer.

The reasons patients drop the treatment include the difficulty of keeping on the regimen (pills must be ingested several times a day under complicated dietary guidelines), its high price (a year's treatment could cost $10,000 to $20,000); drug resistance in some cases, and troublesome side effects, which are just now being explored by researchers.

Side effects include severe nausea, high cholesterol and fatty deposits. And yesterday, a study presented here suggested there is also a worrisome level of kidney stones seen in some patients. The stones disappeared when the patients stopped taking a key HAART drug, indinavir.

Meanwhile, a team of Australian physicians, led by Cooper, said yesterday that key parts of the immune system called CD8 cells are continuing to die off, even in patients on HAART. They said they've found that small quantities of viruses hidden in tissue continue to replicate despite the drugs, sending copies into neighboring tissue.

Pharmacologist Jean-Pierre Sammaossi of the University of Alabama in Birmingham said in a speech yesterday that a key part of the problem in some patients is that the HAART drugs aren't as efficient as they should be in getting to the disease. Either they aren't being absorbed through the stomach in proper amounts, he said, or they aren't being chemically altered within the body to make them as effective as they should be.

What is to be done?

Scientists Joep Lange, Frank DeWolf and Jaap Goudsmit of the University of Amsterdam said yesterday that radical steps are needed to make combination therapy even more effective. They said they're tracking eight patients who have in the last year been given five drugs at once, rather than the normal three.

This therapy includes four drugs that attack the virus' reverse transcriptase module, blocking its ability to make copies of its genes, and one that inhibits a key molecule called protease that's essential to packaging the virus in an infectious form. Within four to six weeks, the combination drove viral levels down below the limits of detection, the Dutch scientists said.

Normal HAART therapy includes the use of three drugs, one a protease inhibitor.

"We are almost a year on the five-drug combination with some patients," DeWolf said. "Tolerance is good. Compliance is extremely good because these are volunteers - they want this."

Lange said the five-drug study reflects his golden rule of HIV treatment: "To get a durable response, suppression of viral replication must be at the lowest level possible."

The Dutch scientists also made public an experiment that targeted hidden viruses in the body by activating the entire immune system at once, including latent immune system T cells.

In the experiment, two HIV patients were injected with a molecule that mimicked the type of immune system attack that a patient suffering the flu, measles and a bacterial infection, all at once, might experience. "The patients had serious side effects" similar to the symptoms of flu and measles over the short term, DeWolf said, but viral levels dropped further.

And both men will go through the experience again to see if they'll drop further, Lange said.

Many scientists have suggested that hope rests with finding ways to prevent HIV from infecting cells. HIV uses two receptors on the surface of cells as doorways - CCR5 and CXCR4. Several studies presented yesterday show that the first virus in a person's body is usually a CCR5-using HIV. But after years of infection HIV mutates, becoming a CXCR4-using virus. And that leads to a deterioration in the patient's health, AIDS and death.

Researcher Kuan-teh Jung, of the National Institutes of Health in Bethesda, Md., presented evidence that HIV contains a gene that suppresses the CXCR4 mutation switch. Perhaps, he said, a drug based on that gene could be given as a treatment that would prevent AIDS in HIV patients.

Also promising is the Salk Institute's Dominique Schel's compound called AMD3100. The drug completely blocks CXCR4, resulting in a 100 percent elimination of viral infection of those cells, Schel reported. It has not been tested clinically.

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