SCIENTISTS EXPLORE METH'S ROLE IN IMMUNE SYSTEM

Reports that a New York man may be carrying a rare and possibly virulent
strain of H.I.V. have focused new attention on the biological relationship
between the virus and methamphetamine, a drug that has become increasingly
entwined in the spread of sexually transmitted diseases in cities from San
Francisco to Miami to New York.

Although methamphetamine, often called crystal meth or speed, is most
troubling to health officials because of its role in blotting out
inhibitions and fueling high-risk sexual behavior, experts say they are
also grappling with mounting evidence that the drug by itself may increase
a person's susceptibility to infection by crippling immune function and
facilitating disease transmission.

"There seems to be something about methamphetamine that predisposes people
to H.I.V. infection," said Dr. Grant Colfax, co-director of the H.I.V.
epidemiology biostatistics and intervention section at the AIDS office of
the San Francisco Department of Public Health. "When we look at why
methamphetamine is increasingly responsible for the H.I.V. epidemic, I do
think we need to look more closely at whether it is somehow suppressing
immunity and increasing viral loads."

The National Institute on Drug Abuse has increased its funding of research
on methamphetamine - including studies looking at how it interacts with
H.I.V. - to $37 million in 2004 from $27 million in 2003.

Knowing what, if any, direct impact the drug may have on the virus has
gained a sense of urgency in recent months. Nationwide, methamphetamine
addiction has become the second most frequent reason for seeking substance
abuse treatment, behind alcohol. And experts fear that more and more
people, particularly gay men, are relying on the stimulating effects of the
drug - in many cases combined with Viagra or other similar drugs - to
engage in unprotected sex with multiple partners.

The man reported by health officials in New York to be carrying a rare
strain of H.I.V. is believed to have used methamphetamine.

A long-term study of more than 4,000 gay men sexually active with more than
one partner recently found that the odds of contracting H.I.V. climb
substantially while using crystal meth, independent of other risk factors.

About a quarter of the men who were followed said that they had used
crystal meth in the six months before the start of the study. They were all
H.I.V. negative when it began.

By the end of the study, called the Explore Project, about 2.1 percent of
the men had become infected. Unprotected sex with multiple partners was
strongly associated with infection. But even after the researchers
controlled for those behaviors and others, like injection drug use, the men
who were taking crystal meth were twice as likely to contract H.I.V.

"This was a really surprising finding," said Dr. Colfax, a principal
investigator on the study. "There's reason to think there's a combination
of factors involved."

One of them may be crystal meth's impact on immune cells. Although research
is limited, studies in animals and on cell cultures have found that
methamphetamine suppresses killer T cells, a type of white blood cell that
fights off pathogens.

That, combined with the drug's tendency to dry out mucosal membranes and
cause abrasions in the mouth and rectum, might slightly increase a person's
vulnerability to infection, said Dr. Antonio Urbina, the lead author of a
study on crystal meth and H.I.V. that appeared last year in the journal
Clinical Infectious Diseases.

In those who are already infected, crystal meth may take a greater toll.
Studies have found that it can interfere with antiretroviral medications
and set off a surge in viral loads, accelerating the progression of the
disease and making a person more infectious to others.

In a study published in the journal Infectious Diseases last year, for
example, researchers looked at 230 people who were H.I.V. positive,
two-thirds of them either former or active users of crystal meth.

Compared with other subjects, those who were regularly using crystal meth
and were also on an antiretroviral medication had far higher viral loads.

Dr. Igor Grant, an author of the study, said one possibility was that the
crystal meth users had failed to adhere to their treatment regimens, as
often happens with drug abusers. But stopping and starting a medication can
be deadly in its own right, other experts point out, because it allows drug
resistant strains to emerge, similar to what occurs when antibiotics are
not taken properly.

"If you're a person who is not adhering to your diabetes medication, that's
one thing because you can hurt yourself but not others," said Dr. Roger J.
Pomerantz, an AIDS specialist at Thomas Jefferson University in
Philadelphia who studies interactions between drugs and the virus. "But
with this you can hurt others by increasing the likelihood of both
transmission and drug resistance."

In studies, Dr. Pomerantz has found that although substances like heroin
and alcohol also appear to increase viral replication, others, like
caffeine, can actually reduce it.

Whatever crystal meth's influence on the immune system and viral
replication turns out to be, experts stress that its most alarming impact
is on behavior.

"I think that's really the biggest gorilla in the room," said Dr. Steve
Shoptaw, a research psychologist at the University of California, Los
Angeles, Integrated Substance Abuse Programs. "Being in a sex club for 36
hours on crystal meth and engaging in unprotected anal sex is really the
most profound effect."