The San Francisco Examiner - Wednesday, May 7, 1997
Lisa M. Krieger, Examiner Medical Writer

There is no evidence that HIV has been cleared from any patient. For patients with drug resistance or long-term complications of therapy, that goal may be unattainable. It is also out of reach for patients who cannot afford the expensive drugs.

But the new work - based on a mathematical calculation of the viral life cycle by Dr. David Ho of the Aaron Diamond AIDS Research Center at Rockefeller University in New York and published in Wednesday's journal Nature - suggests that the day will come when aggressive anti-viral treatment prevents infection of new cells and existing HIV-infected cells slowly die off. At that point, the virus would be vanquished.

"It would be wrong to believe that we are close to a cure for AIDS," writes Ho. "However, the recent advances in treatment and pathogenesis do warrant a close examination of the feasibility of eradicating HIV from an infected person."

Plenty of researchers have ventured opinions of how long treatment must persist to eliminate the AIDS virus, which has eluded a cure since its discovery in 1981. The viruses that cause cold sores and chicken pox, for example, are life-long visitors.

But new research findings shine new light on the subject, offering hope to patients.

One study, published in the same issue of Nature, concludes that HIV infection is sustained by relatively few infected cells.

The team of Dr. Robert Siliciano of Johns Hopkins University looked at the lymph nodes of treated patients and found that fewer than 0.05 percent of immune cells harbored DNA of the virus. But these few viral particles pack a big punch: When stimulated, these cells were capable of producing the virus.

"These cells can survive for months or years," cautioned Siliciano. "They represent a potential barrier for curing the infection."

A second study by Ho and his colleagues explored what would eventually happen to these "holdouts." They observed that anti-viral treatment causes a two-phase reduction in HIV. Levels of the virus plummet almost immediately after treatment is started, but then decline much more slowly.

They determined the life span of these slow-to-die cells in the second phase of decline and estimated that 2.3 to 3.1 years of treatment with an aggressive anti-HIV regimen might be able to eliminate all virus.

But that time could be much longer if the virus is hiding in well-protected parts of the body.

Until recently, treatment produced only a slight delay in the relentless progression from HIV infection to AIDS. But scientists discovered that combining several anti-viral treatments could stop the advance and dramatically suppress the virus in the bodies of many patients.

Experts warn that only time will tell whether there may be a third phase of viral infection with hidden and yet more-slowly dying cells - or whether there is some sanctuary, far from the reach of drugs, that permits HIV to reside forever. There is the more remote possibility that fragments of the virus' residual DNA could recombine and generate deadly new virus.

The only real way to see if the virus has been eradicated in patients is to stop therapy and see if it comes back.

The Aaron Diamond team has not asked patients in the study to quit treatment.

Some San Francisco doctors who have asked patients under their care to stop taking anti-viral drugs after one year say they observed a rebound of infection.

"A blunt personal view is never to think that you've outsmarted HIV: It should be obvious if, and when, eradication is achieved," wrote Dr. Simon Wain-Hobson of the Pasteur Institute in Paris in an accompanying editorial in Nature.

"HIV can clearly be put down by therapy," he wrote. "So might it even bow out? Cross your fingers."
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