At last, the AIDS virus may be in retreat. In the past two years, companies have developed drugs powerful enough to render a patient's blood virtually virus-free. With the bug held in check, victims have seen remarkable recoveries in their ravaged immune systems. Death rates and hospital admissions for the myriad infections that accompany AIDS are plunging, at least in countries rich enough to afford the treatments, which can cost as much as $15,000 annually for each patient.
Now comes more good news. In a paper in the May 8 issue of Nature, Dr. David Ho of the Aaron Diamond AIDS Research Center and Alan Perelson of Los Alamos National Laboratory use mathematical models to show that in theory, combining the use of protease inhibitors with other drugs like 3TC and AZT, the AIDS virus could be completely eradicated after as little as 2.3 years of treatment. Ho's study and two others--one in the same Nature and another in the May 9 Science--also show that drugs are attacking the virus even in hidden reservoirs such as the lymph nodes.
But despite the progress, crucial problems remain. For one thing, the new therapies may not fully restore patients' battered immune systems. This means that even patients whose infection is kept in check or eradicated may still not be able to fight off certain illnesses on their own. Whether gaps in the body's defenses remain "is an absolutely critical question, but we don't know the answer yet," says Mark Jacobson, associate professor of medicine at the University of California at San Francisco. What's more, the new therapies leave HIV genes lurking in cells. One of the new studies shows that as long as the cells remain alive, these genes can be turned on, rekindling the disease. "The situation is neither black nor white," Ho warned colleagues at a conference last winter. "We must paint it in the proper shade of gray."
Indeed, HIV has an uncanny ability to hide. When doctors first began to combine the new protease inhibitor drugs with older AIDS medicines, they were able to reduce the level of HIV in the blood of infected patients to below the limits of detection in many cases. Now, in the Science paper, a team led by Ashley T. Haase of the University of Minnesota Medical School reports that six months' treatment with a trio of drugs cleared more than 99.9% of detectable viral particles from the tonsils of 10 patients. What's more, it happened faster than expected. "We anticipated they would hang around for a long period of time," says Haase. "But half were cleared in a day."
IN HIDING. Unfortunately, though, not being able to detect the virus doesn't mean it's not there. Duke University pediatrician and AIDS expert M. Louise Markert warns that if just one or two viral particles survive, they can rekindle full-blown AIDS. "So far, everyone who has gone off medication has [seen the virus] bounce back," says Warner C. Greene, director of the Gladstone Institute of Virology & Immunology. Adds Dr. Calvin J. Cohen of the Community Research Initiative of New England: "Many of us fear that the punch line is that HIV will not go away."
An even bigger long-term challenge may be dealing with patients who become AIDS-free but are left with damaged immune systems. Normally, the human immune system contains cells programmed to respond to specific invaders such as influenza. But a recent study by National Institutes of Health immunologists H. Clifford Lane and Mark Connors shows that after treatment with the triple therapy, AIDS patients are missing some of these specific cells. There are also case reports of individual patients who continue to get infections characteristic of AIDS even after their immune-system cell counts have been boosted. It's possible that those who survive AIDS will be left with key gaps in their immune systems' function, leaving them vulnerable to other diseases, including cancer.
The prospect of damaged immune systems has some scientists contemplating drastic steps. At Duke, for instance, Markert and her co-workers have begun transplanting thymuses into AIDS patients in the hope that the new gland will generate immune system cells to plug the gaps. The data aren't in yet, but one thing is clear: Winning the final siege against the AIDS virus is still a formidable challenge.