METHADONE PROMOTES HIV INFECTION IN CELL CULTURE STUDIES AT THE CHILDREN'S
HOSPITAL OF PHILADELPHIA

UTRECHT, Netherlands, May 16 - 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.