Penn, Wistar researchers thwart HIV without antiviral drugs

Wistar's Luis Montaner led the immune- therapy study.
Wistar's Luis Montaner led the immune- therapy study.
Posted: March 08, 2012

For the first time, researchers have shown that they can suppress the AIDS virus by bolstering patients' immune systems, while taking them off standard antiviral drugs.

The small, six-month-long study, led by scientists at the Wistar Institute and the University of Pennsylvania, put patients on interferon, an old drug with nasty side effects. Interferon by itself had not worked against HIV, the virus that causes AIDS, in previous studies. The researchers can only speculate about why their protocol - which initially gave antivirals and interferon together - was effective.

Still, the study offers tantalizing evidence that an immune system damaged by HIV can nonetheless be prompted to control the virus on its own - without the powerful antiviral drugs that keep the microbe from reproducing.

While antivirals have transformed HIV infection from a death sentence into a manageable disease, they are costly, must be taken for life, and can spur the virus to develop drug resistance.

The new study was "designed to answer the question: Is it possible to control the virus with immune therapy? The answer is yes," said Wistar immunologist Luis Montaner, who presented the results Wednesday at an international AIDS conference in Seattle. "There have been a lot of false hypotheses, so people are very jaded. But I firmly believe this gives us hope that one day we can control HIV in the absence of" antiviral therapy.

Virologist Satish Pillai, an AIDS researcher at the University of California San Francisco who was not involved in the study, called the findings "really amazing." The implication, he said, is that the body has natural defenses against the virus that are just waiting to be tapped by the right therapy.

At the National Institutes of Health, which funded the study, AIDS expert Carl W. Dieffenbach had a more reserved reaction.

"It's an important first step, so I don't want to damn it with faint praise," said Dieffenbach, director of the division of AIDS. "But I don't want to oversell it, either. While I suspect that the response to interferon was far more than we would have expected, we can't be sure."

Interferon, a drug based on a protein naturally produced in the body, is used to treat hepatitis C and some cancers. Side effects include flulike symptoms, hair loss, and depression.

In the new study, 20 patients took antiviral drugs plus interferon for five weeks, then interferon alone for up to 24 weeks. Any patient whose "viral load" - the amount of virus in the blood - surged above a low threshold was immediately put back on antivirals.

Based on previous studies in which patients tried taking breaks from antiviral treatment, the researchers predicted HIV would surge within about a month in all but a few of the patients.

Instead, nine patients - 45 percent - suppressed the virus on interferon alone. Three patients kept HIV in check for 12 weeks, while six patients were still suppressed at the end of the 24-week study.

Even more encouraging, sophisticated DNA tests showed that seven patients had a significant decrease in the amount of HIV hiding in their T cells, the immune cells that the virus invades and hijacks to reproduce. Normally, this reservoir of "integrated" HIV would start churning out more virus copies as soon as antivirals were stopped.

"Generally, we've assumed the integrated HIV is silent and invisible" to the immune system, said Una O'Doherty, a transfusion medicine specialist in the University of Pennsylvania's pathology department who conducted the DNA tests. "Maybe it's not invisible."

Interferon was shelved for HIV long ago, when antivirals revolutionized therapy. So why did it suppress the virus in the new study?

Montaner speculated that the key was the five weeks of overlapping treatment. Perhaps the antivirals gave interferon a chance to prime the immune system for defensive action, much like a vaccine primes the system to prevent infection.

UCSF's Pillai, who had studied interferon in patients co-infected with HIV and hepatitis C, believes the drug boosts "restriction factors" - immune-system chemicals that help neutralize or divert viruses.

In any case, the quest for therapies that work on the immune system - as opposed to the virus - is growing. At least seven companies and many academic labs are pursuing vaccines, gene therapies, or other immune boosters that would suppress HIV without necessarily eradicating it, a so-called functional cure.

Cure is a heady term, but it is theoretically possible, as a patient living in Berlin has shown. He has been free of the virus since 2008, following a bone-marrow transplant to treat leukemia, because the marrow came from one of the rare Northern Europeans who has a natural genetic resistance to HIV infection.

For Montaner's team - 14 scientists from seven institutions, including Philadelphia Fight, which helped enroll research subjects - the next step is finding funding for a larger trial.

"When the study was started, it was expected by most people to fail," he said. "Now, everyone is intrigued and hopeful."


Contact Marie McCullough

at 215-854-2720 or mmccullough@phillynews.com.

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