By Steve Sternberg

USA Today 27 Nov. '00

Experimental research with monkeys helps explain why three-week holidays from anti-HIV drugs appear to bolster the immune system and permit it to control the AIDS virus.

"This study represents the first evidence that treatment interruptions make a difference, both in terms of the immune system and of viral control," says Franco Lori of the Research Institute for Genetic and Human Therapy in Washington, D.C.

Lori's team found that treatment interruptions arm key immune system cells, called killer T cells, to attack and destroy HIV.

The process works this way: When HIV goes untreated, the virus simply overwhelms the immune system. Hitting the virus hard with drugs early in the infection safeguards the immune system. Alternating treatment with drug holidays keeps virus levels low and permits the immune system to attack HIV.

Lori and collaborator Julianna Lisziewicz have developed a test of killer T cell function. The test, Lori says, "directly measures the immune system's ability to control the virus."

The work reflects a trend in AIDS research -- finding cheaper, simpler and more effective ways to treat AIDS using available drugs.

Lori, Lisziewicz, Bruce Walker at Massachusetts General Hospital in Boston and Clifford Lane at the National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Md., among others, hope to accomplish that goal by strengthening immunity.

Walker reported in September that treatment interruptions work in a small number of humans, but the study didn't explain why they work. "But it's very difficult to study the mechanisms in humans," NIAID director Anthony Fauci says. "Tissue isn't easily available, and it's tough to get people who are truly (newly) infected."

Unless people are newly infected, their immune systems may be too damaged to rebound after treatment.

The monkey study supports Walker's finding that treatment interruptions help the immune system. "The monkeys show that very clearly," Lori says. "Every time there's a treatment interruption, the immune system becomes stronger and stronger. Eventually, it is able to control the virus without therapy."

The report, in the current issue of Science, involves three groups of monkeys. One group of six monkeys was treated continuously with antiviral drugs. Another group alternated between three weeks on drug therapy and three weeks off. A third group received no treatment.

"The group that received continuous therapy did not mount any immune response against the virus," Lori says. "The group that received intermittent therapy had a very strong, virus-specific immune response."