In a new study, drug treatment interruptions have for the first time been shown to boost HIV-specific immune responses in chronically infected patients as compared to a matched control group. Indeed, one patient in the study who had stopped taking medication was able to control his viral infection without drugs for at least four months after reinitiating and then permanently stopping drug therapy. A report on the findings by scientists at The Wistar Institute appears in the September issue of the Journal of Infectious Diseases.
The current standard of care for HIV patients involves combinations of three or four drugs that suppress the virus, often to undetectable levels. Although highly effective, the therapeutic regimen is demanding and accompanied by sometimes debilitating side effects.
Other more sustainable approaches to treatment for HIV infection are needed, and the new findings suggest that HIV patients may be able to use structured treatment interruptions (STI) as a tool to strengthen their immune systems, perhaps dramatically. The clinical implications could be significant, and a clinical trial is currently recruiting volunteers to test the concept.
The hypothesis behind STI is that, following the immune recovery seen in patients under drug treatment, a controlled stop-and-start strategy might coax the immune system to develop an increasing capacity to control HIV infection. The approach offers the possibility that continuous drug therapy could someday become a thing of the past. Today’s means - drugs - might become a mere agent to manage the real hero - the immune system - to effect the end: continuous suppression or, ultimately, eradication of HIV.
"While many patients would benefit from occasional breaks from drug therapy and its side effects, we are pursuing whether short interruptions in therapy can also act to instruct the immune system to control the virus, perhaps to a point where treatment will not need to be reinitiated," says Luis J. Montaner, D.V.M., D.Phil., an assistant professor at The Wistar Institute and senior author on the new study. "The virus would likely not be eradicated in these patients, but is expected to be fully controlled by the immune system without the toxicity associated with current drug therapies."
For the observational study, Montaner and his team recruited 10 AIDS patients. Five of the participants agreed to be monitored while, at their own discretion, they interrupted their medication for a median period of eight weeks. The five control patients were not on any medication.
All five experimental patients showed significant increases in anti-HIV immune response during the interruption periods. The most striking response came with a patient identified as C-13, a chronically infected Caucasian man in his 40s. Diagnosed with HIV in 1987, he had been on a drug combination for three years before entering the study. After reinitiating medication for two months, he decided to stop - for good. In the months that followed, his immune system responded even more powerfully against the HIV virus. When last checked four months later, his virus levels remained very low.
Patient C-13’s experience is reminiscent of the report published in May 1999 in the New England Journal of Medicine, describing 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.
Montaner’s co-authors on the new study are located at The Wistar Institute, the University of Pennsylvania, the Philadelphia Field Initiating Group for HIV-1 Trials (Philadelphia FIGHT), and the Aaron Diamond AIDS Research Center.
Support for the study was provided by Mrs. Martha Miller, the Campbell Foundation, the Robert I. Jacobs Fund of The Philadelphia Foundation, and the John M. Lloyd Foundation. Funding for the clinical trial was provided by the National Institutes of Health.
The Wistar Institute is an independent nonprofit biomedical research institution 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 focused on basic research. Founded in 1892, Wistar was the first institution of its kind devoted to medical research and training in the nation.
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