Rooting out dormant HIV-infected cells.

Current AIDS treatments can kill off virus to nearly undetectable concentrations. Nonetheless, scientists have been unable to wholly eradicate HIV, the virus that causes AIDS, in any patient.

HIV infects immune cells called CD4 T cells. In a CD4 cell that the immune system hasn't called into action, HIV can lie dormant for years, hiding from anti-AIDS drugs while retaining the potential to replicate.

In an effort to drag these hibernating cells out into the open, where medication or healthy immune cells might destroy the virus, scientists have now employed interleukin-2 (IL-2). In some patients, this immune-system protein that activates CD4 cells appears to flush the infected cells from hiding, report researchers led by a group at the National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Md.

The scientists gave 26 HIV-infected patients a combination of anti-AIDS drugs; 14 also received IL-2. Because IL-2 can cause nausea, fatigue, and headaches, physicians gave patients their doses of that protein intermittently over a period of 16 to 51 months. Nearly all the patients had previously received some anti-AIDS therapy, and all started the study with low viral blood concentrations, or counts.

After treatment, the researchers cultured patients' blood cells to increase the number of CD4 cells. No virus turned up in three of the patients treated with IL-2, even though more than 100 million CD4 cells were examined in each, the scientists report in the June NATURE MEDICINE. Although the virus remained detectable in the other IL-2 patients, they had lower viral counts than the 12 participants not getting the protein.

The scientists obtained lymph node tissue samples from two of the people in whom the virus was undetectable. The CD4 cells collected, even after being cultured, also seemed to harbor no virus.

However, when these two patients later went off anti-AIDS medication, the virus showed up again, says coauthor Tae-Wook Chun, a virologist at NIAID. The third patient who had no detectable virus stayed on anti-AIDS medication and still shows no virus.

While encouraged, Chun remains cautious. "Just because you knock the reservoir [of virus] down to a low level, it doesn't mean you have eradicated it," he says. Rather, these findings support evidence that HIV is lurking in other immune cells or in CD4 cells in hard-to-reach places in the body, Chun says.

The brain, the eye, and the testes all have barriers that keep out many blood-borne immune cells and proteins. Anti-AIDS drugs "don't penetrate those regions very well," says Roger J. Pomerantz, a virologist at Thomas Jefferson University in Philadelphia. Semen can harbor HIV capable of replicating, even as tests show that HIV in the blood has fallen below detectable concentrations in response to anti-AIDS drugs, he says. Such compartmentalization could thwart IL-2, which is carried in the bloodstream.

"We clearly need some approach to purging these [HIV] reservoirs," says Warner C. Greene, a molecular virologist at the University of California, San Francisco. The new study "represents the first promising effort," even though it doesn't indicate how IL-2 might work in people carrying a lot of virus, he says.

"My concern is that, in the future, it may be difficult to find [patients with] such low viral burdens, even on medication," Greene says. He and his colleagues have already begun to observe HIV resistance to drugs in San Francisco patients. In response, viral counts may soar. "I think we're in a window of time, a honeymoon, where the drugs remain quite effective throughout the population."