News Release

Clinical trial will test controlled 'drug holidays' to counter HIV

Peer-Reviewed Publication

The Wistar Institute

Researchers have received approval for a new clinical trial to test carefully controlled interruptions in HIV patients' drug regimens as an approach to boosting their immune systems, eventually to the point where they can manage their infections without the need for drugs. Patient recruitment will begin immediately for the trial, which was conceived by a team of scientists headed by Luis J. Montaner, D.V.M., D.Phil., an assistant professor at The Wistar Institute, and will be overseen by clinicians in the University of Pennsylvania Health System.

Current state-of-the-art therapy for HIV infection is to administer a cocktail of three drugs that suppresses the virus, often to undetectable levels. While the treatment, known as Highly Active Anti-Retroviral Therapy, or HAART, is very effective, it is too expensive to represent a worldwide solution to the problem of HIV and AIDS. It is also complex and burdensome for patients to adhere to, and it is often accompanied by disturbing, potentially dangerous side effects. While patients are under therapy, however, the number of viruses in their blood drops, and the immune system recovers its ability to respond.

Researchers at The Wistar Institute and elsewhere believe that carefully structured "holidays" from the drugs - known as intermittent HAART - might lead, in effect, to autovaccination against HIV. Patients' ability to mount a response to their own virus has been observed by Dr. Montaner and his colleagues in a subset of chronically infected patients who had maintained long-term viral suppression with their medications before a controlled interruption of treatment. The present trial will test the capacity of these responses to control HIV without medication.

"Many people feel that the answer to AIDS will be found in improved antiviral drugs," says Dr. Montaner, principal investigator on the scientific study that led to development of the new trial. "Immunologists like myself, however, see in the drugs an opportunity to use them for eliciting a long-term immune response that ultimately might be able to control the virus. HIV-infected people carry the seeds of their own cure, we believe."

The hypothesis behind intermittent HAART is that, following the immune recovery seen in patients under treatment, a controlled stop and start strategy might coax the immune system to develop an increasing capacity to control HIV infection after each treatment interruption cycle. The hope is that, after a limited number of such cycles, a state of balance between the immune system and HIV will be achieved, with the immune system successfully maintaining low viral loads without further need for drugs.

The trial does have risks for participating patients, the researchers note.

"As an unproven experimental approach for controlling HIV, potential side effects such as the emergence of viral resistance or an acceleration of disease progression will be carefully monitored," says Jay Kostman, M.D., principal clinician for the trial and Chief of the Division of Infectious Diseases at Presbyterian Medical Center in the University of Pennsylvania Health System.

There is encouraging anecdotal support for the idea. In addition to Dr. Montaner's observations over the last two and a half years, a report published in May 1999 in the New England Journal of Medicine describes a recently infected patient in Berlin who started and stopped therapy several times because of medical complications. Today, that patient's HIV infection has been under control without drugs for about two years. The present trial will focus on the potential for chronically infected persons to respond in a similar manner.

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The Wistar Institute is an independent nonprofit biomedical research organization dedicated to discovering the basic mechanisms underlying major diseases, including cancer and AIDS, and to developing fundamentally new strategies to prevent or treat them. The Institute is a National Cancer Institute-designated Cancer Center - one of the nation's first, funded continuously since 1968, and one of only 10 devoted to basic research. Founded in 1892, Wistar was the first institution of its kind devoted to biomedical research in the nation. News releases from The Wistar Institute are available to reporters by direct e-mail, fax, or U.S. mail upon request. They are also posted electronically to Wistar's home page (ttp://www.wistar.upenn.edu) and to EurekAlert! (http://www.eurekalert.org), an Internet resource sponsored by the American Association for the Advancement of Science.


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