Latent AIDS found in patients New drugs diminish but don't eradicate infection, Fauci says

September 16, 1997|By Jonathan Bor | Jonathan Bor,SUN STAFF

Casting doubt on prospects for an AIDS cure, a leading researcher said yesterday that patients whose viral levels have been pushed to undetectable levels months after starting drug therapy actually harbor a silent infection in "resting cells" of their immune system.

Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said the existence of a "latent reservoir" of infection suggests that the virus might rebound to dangerous levels if patients ever stopped taking their medications.

"I'm quite skeptical about how long it's going to be before we can actually stop the drugs," said Fauci, who helped open a weeklong conference being held by the University of Maryland's Institute for Human Virology in Baltimore. "I'm not sure we can ever stop."

The conference, organized by institute director Robert C. Gallo, has attracted close to 1,000 researchers from around the world. Yesterday's was the 25th time the annual "Gallo meeting" has been held, but just the second since the AIDS researcher left the National Cancer Institute and opened laboratories in Baltimore.

Fauci's results dampen hopes that the new drug combinations -- made possible two years ago by the introduction of protease inhibitors -- could eventually eradicate the virus from a person's blood and tissues, thus achieving an outright cure.

Evidence of a silent infection stems from a study of 13 patients who had been taking the drugs for about a year. Nine of the patients had undetectable levels of the human immunodeficiency virus (HIV) in their bloodstream, a result that has been seen in thousands of AIDS patients who have been taking the drugs.

But in all nine patients, Fauci found evidence that the virus was hiding out in "resting cells" of the immune system. These are white blood cells -- known as CD4 T-cells -- that have gone into an inactive state, waiting months or even years to "switch on" and make new copies of the virus.

Anti-viral drugs are capable of suppressing the virus in cells that are producing copies of HIV and releasing them into the bloodstream -- but not in cells that are at rest.

"We're not in the mode of being able to eradicate those cells," Fauci said. One approach could be a drug that would "switch on" the resting cells, making them targets for protease inhibitors and other anti-viral drugs.

Another scientist who has been studying the problem of latent infection, Dr. Robert Siliciano of the Johns Hopkins School of Medicine, is scheduled to address the conference Thursday.

The idea that the drugs could cure someone of AIDS has been championed by Dr. David Ho, a well-known researcher in New York who plans to take several patients off their drugs and then monitor them for any signs of resurgent virus. Employing a mathematical model, Ho said the virus could be eradicated in three years. His patients are about two years into treatment.

But Fauci said the projection of a three-year cure was based on the mistaken assumption that "you can completely shut off viral replication."

But as long as resting cells harbor infection, he said, the potential for replication remains. The problem is that resting cells are long-lived. Nobody knows how long they can survive, but he said it is not unreasonable to think that they could survive for many years -- escaping the continual assault of drugs.

Ho, who directs the Aaron Diamond AIDS Research Center, could not be reached for comment yesterday.

Gallo said the findings only strengthen his conviction that recent progress with AIDS therapies should not lull people into the mistaken belief that the disease has been beaten.

Acknowledging that drug combinations have brought about some remarkable improvements, he said they are beset with several problems: Their cost puts them beyond the reach of 95 percent of the people who need them around the world, and some patients who can afford them cannot tolerate their side effects.

Many patients have trouble complying with complicated dosing schedules. And it is too early to determine whether the drugs will encourage the growth of resistant strains.

"Protease inhibitors have made the single most important difference," Gallo said. "But it is too early to open champagne bottles."

Gallo's institute has been working on so-called biologic approaches to AIDS -- ones intended to manipulate a person's immune system to fight AIDS rather than dousing the virus with toxic chemicals.

While the findings darken prospects that existing medications can eradicate the virus, they do not mean that the drugs cannot help people manage their disease for long periods of time.

"I'm less pessimistic about being able to have a very positive and favorable impact on people," he said. "The difficulty is that over the long haul you're going to have to take into account some real-life situations that clinical studies generally don't address."

Side effects that may be tolerable in the short run could become more serious as the years progress, he said. The problem of drug resistance could be managed by switching patients from one protease inhibitor to another.

"We're better off than we've been in the past but we should not stop and think that victory is here," Fauci said.

Pub Date: 9/16/97

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