Studies Find AIDS Virus ‘Hides’ in Lymph System

In studies that may help unravel the mystery of why people infected with the AIDS virus live for years without developing symptoms, scientists have found that the virus--rather than being inactive during the early stages of infection--hides in the lymph system, where it is busy multiplying before it wages war on the body.

The findings, reported in two papers published in today’s issue of the journal Nature, challenges the widely held belief that the human immunodeficiency virus is latent before the patient develops AIDS.

“The conclusion clearly is that HIV disease is active and progressive throughout the entire course of infection,” said Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Disease and co-author of one of the papers. “We have to start rethinking the concept of what we mean by latency.”

Dr. Ashley T. Haase of the University of Minnesota, who co-authored the second study, said his research showed a “massive covert infection (in the lymph system). . . . We discovered that there were these enormous numbers of these . . . infected cells that we had never seen before.”

The findings will help scientists better understand the path that HIV infection takes and may also play an important role in developing new therapies and drugs to treat patients, the authors said.

Although the research clearly suggests that treatment should begin as soon after infection as possible, drugs that would combat the disease during its earliest stages are just now being tested and may not be available for some time, Fauci said. Doctors say it may not be wise to prescribe antiviral drugs such as AZT immediately after infection because they are toxic and patients develop resistance to them.

The new studies also may have implications for the design of vaccines being developed to prevent HIV infection, said Haase, who added that any vaccine would have to target billions of infected lymph cells. But because many of those infected cells are not actively producing the virus, they would be difficult to detect.

“That may or may not be possible,” he said, “but it is certainly a more formidable problem than we realized.”

Indeed, experts say the new findings once again demonstrate the complexity of HIV and the difficulties of finding effective treatments and a cure.

“These studies demonstrate the tremendous capacity of the body to hold on to HIV,” said Jay Levy, an AIDS researcher at the University of San Francisco. “The challenge for a cure is very, very difficult.”

The idea that the AIDS virus resides in the lymph system is not new. But Fauci and his colleagues are the first to track the course of infection in both blood and lymph samples and are the first to demonstrate the extent to which the lymph system is affected by the virus.

For each of 12 patients in various stages of disease, the Fauci group analyzed the numbers of HIV-infected cells and watched how quickly the virus multiplied.

According to Fauci, when a person is infected with HIV, the virus replicates rapidly and disseminates, seeding itself in lymph organs such as the tonsils, spleen, adenoids and lymph nodes. He said that in the early stages of infection, his studies showed 10 times more virus in the patients’ lymph nodes than could be detected in their blood.

“The virus sort of gets sucked out of the blood into the lymph nodes and is trapped” inside cells designed to filter viruses out of the blood, he said. Eventually, HIV destroys these filter cells, leading to the deterioration of the immune system and the onset of the lethal stage of AIDS.

The Haase study, which employed sophisticated methods of examining individual lymph cells, confirmed Fauci’s findings that the virus thrives inside the lymph system.

But Haase found that only a small portion of the infected cells--about 1%--are capable of replicating the virus. The remainder of the cells act as “a reservoir of infection,” fueling the virus-producing cells. He estimated that there are up to 100 billion of these so-called latently infected cells and up to 1 billion “productively infected” cells in an infected person.

“I liken it to a constantly erupting volcano,” he said, “with latently infected cells feeding the productively infected ones.”