Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

Reuters NewMedia, Inc. - Tuesday, 19 November 1996.
Maggie Fox

Better treatment is translating directly into empty hospital beds. The "opportunistic infections" that characterise AIDS such as Kaposi's sarcoma, a type of cancer, are sometimes fading before the very eyes of doctors.

But the euphoria that greeted the news this summer that the virus had been seemingly eradicated in some patients with a triple dose of strong drugs has now been tempered.

Doctors who whispered the word "cure" are now talking about merely controlling the virus.

In the latest positive study, Dutch researchers found that volunteers treated with a triple combination of drugs cleared the virus not only from their blood but from their lymph glands.

This is important because AIDS experts now believe that up to 90 percent of the virus lurks in the lymph glands, building up strength for its onslaught against the immune system.

"It's encouraging us that we are on the right track," said Sven Danner, professor of medicine at the Academic Medical Centre, University of Amsterdam, who worked on the study.

Danner, whose group tested 33 volunteers, said they found three important things. "The new thing is that in the lymphoid tissue, the viral load is decreased a thousandfold. We also found undetectable viral load in blood and also did not find resistance (to the drugs)."

Danner was cautious, saying the test used on the patients' lymph tissue -- in this case the tonsils -- may not have been sensitive enough.

"I think if you use a more sensitive test, then probably after half a year you will find some virus left," he said.

"I am not sure that it is possible to absolutely eradicate HIV from the body, but nevertheless we are looking at it."

He asked: "If you succeed in getting rid of a virus, is your immune system capable of coming to full restoration? We have the impression that the later you start (drug treatment), the more disturbance of the lymphoid architecture there is."

The next step will be to test the volunteers again after two years of therapy to see if the lymph remains clear.

But here again, researchers run into problems. When he first announced the remarkable results of triple combination therapy in July, David Ho of the Aaron Diamond AIDS Research Center in New York said he was planning to take his first volunteer off the drugs to see if he had indeed been cured.

But he hasn't been able to do so.

"The patient didn't want to go off," Ho said. "He wanted to be conservative, and only go off if the tissues show no signs of infection by the virus."

All of Ho's volunteers are now undergoing tissue biopsies to see if the lymph is clear of virus. They say they will announce their findings in January.

Another problem is that the drugs are ponderous to use, with patients having to take numerous pills at various times of day.

All AIDS experts agree that what they call compliance -- taking the drugs every day at the right time -- is vital. The drugs all start to wear off after just a few hours.

And the drugs are strong.

"It's not always easy to take these three drugs," Danner said. "A quarter of the patients dropped out because of side-effects." These included nausea and diarrhoea.

This is bad news for those with advanced infection. "We have started to see a few failures," said Eric Sandstrom, chief of the AIDS Unit at Soder Hospital in Stockholm.

"We have patients who are advanced in their disease and they hear about these new, aggressive treatments and they want to try them. But they have difficulty tolerating the new combinations. They took too many drugs (in the past). Their viral load goes up and we start to see complications."

Again, however, there could be hope for such patients.

Ho's and Danner's work involves the first generation of AIDS drugs, the nucleoside reverse transcriptase inhibitors, combined with newish drugs known as protease inhibitors.

Both groups used Glaxo Wellcome's AZT and 3TC (Epivir), plus ritonavir (Abbott Laboratories' Norvir).

The drugs attack enzymes important to the virus's replication, each one hitting at a different phase of its cycle.

A newer generation of drugs is showing similar effects.

Known as non-nucleoside reverse transcriptase inhibitors (NNRTIs), they not only add a new weapon to the growing armoury against the HIV virus, but work as well as the protease inhibitors, Julio Montaner of Canada's HIV Trials Network said.

Montaner said the NNRTIs offered new choices to AIDS patients taking one or two drugs who suffered a resurgence of the virus. Once the virus mutates into a resistant form, doctors fear it will resist other drugs in the same class.

But having a new class of drugs to give the patients means they have not used up all their opportunities for treatment.

Doctors say the recent findings add to a growing body of evidence that hitting the virus early and hard is the best way to fight it.

"These new, powerful treatments point to the fact that people who think they are HIV-infected, they should not wait too long before they have themselves tested," Danner said.

"If you wait till you are symptomatic, usually you are in a very advanced stage of disease."
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