Pubdate: Thu, 17 May 2001
Source: United Press International (Wire)
Copyright: 2001 United Press International
Author: Norra MacReady, UPI Science News


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 

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.
- ---
MAP posted-by: Jo-D