May 16, 2001 Utrecht, The Netherlands — Methadone, the drug that is widely used in drug treatment centers to treat heroin addicts, stimulates HIV infection of human immune cells studied in cell cultures, according to immunology researchers from The Children’s Hospital of Philadelphia.
The researchers proposed that HIV-infected patients receiving methadone to treat drug abuse should have their blood and immune status closely monitored for possible adverse effects of the treatment. They reported their results today at an international conference of the PsychoNeuroImmunology Research Society, meeting in Utrecht.
It is well established that intravenous drug users are at high risk for HIV and AIDS. In addition to disease that is spread by HIV-contaminated needles, drugs such as morphine and heroin – classified as opiates – have been shown to stimulate HIV replication in human immune cells. Methadone is a synthetic opiate that shares many biological and chemical properties with morphine and heroin. "Because methadone has been shown to reduce human immune responses, we decided to study its effects on HIV infection of human immune cells," said Wen-Zhe Ho, M.D., an immunology researcher at Children’s Hospital, who presented the research.
Working in cell cultures, the researchers found that methadone increased HIV infection of human microglial cells and macrophages, two important types of immune cells that are reservoirs for the virus in the central nervous system and peripheral tissues.
Furthermore, when added to blood cells taken from HIV-infected patients, methadone changed latent HIV infection to active HIV replication in the cell cultures. Replication is the process by which HIV spreads from infected cells throughout a patient’s body.
The researchers also investigated possible mechanisms by which methadone enhances HIV infection of these immune cells. They showed that methadone has the ability to increase expression of CCR5 receptors on the cell membrane; these receptors provide a method for HIV to enter immune cells. In addition, their study demonstrated that methadone could activate HIV LTR, a promoter that causes HIV infection to switch from latency to an active state.
"These results support our hypothesis that, like other opiate drugs, methadone may raise the risk of HIV infection," said Dr. Ho. "Further investigations should be done to study whether our laboratory results accurately reflect how HIV infection progresses in patients receiving methadone." In their paper, Dr. Ho’s team suggested that HIV-infected patients being treated with methadone should be monitored for changes in HIV viral load and CD4 cell counts, both of which are indicators of disease progression in HIV/AIDS.
In addition to Dr. Ho, other co-authors from Children’s Hospital were Yuan Li, M.D., Xu Wang, Sha Tian, and Steven D. Douglas, M.D. The study was supported by the National Institutes of Health.
Founded in 1855 as the nation's first pediatric hospital, The Children’s Hospital of Philadelphia is ranked today as the best pediatric hospital in the nation by a comprehensive Child Magazine survey. Its pediatric research program is among the largest in the country, ranking second in National Institutes of Health funding.
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