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New AIDS Drugs Aim to Block Virus at Cell's Door

Current treatments only work after a cell has been infected

SATURDAY, July 13, 2002 (HealthDayNews) -- The virus that causes AIDS can be extremely difficult to control once it invades the body, and even the most powerful drugs only try to prevent its spread after cells have been infected.

But researchers are developing new drugs that aim to block the virus from piercing cells in the first place.

None of the most anticipated drugs will be ready for pharmacy shelves in the near future, and experts aren't sure if they'll revolutionize HIV treatments the way the so-called "drug cocktail" regimens did in the mid-1990s.

Still, there's plenty of hope that they will give doctors new weapons against an elusive enemy.

"They're certainly looking very encouraging," says Dr. Daniel Douek, chief of the human immunology section at the Vaccine Research Center of the National Institutes of Health.

During the last six years, the U.S. death rate from AIDS has fallen dramatically since the introduction of the "drug cocktails." The estimated annual number of AIDS-related deaths fell approximately 70 percent from 1995 to 1999, from 51,117 deaths in 1995 to 15,245 deaths in 2000, according to federal health statistics.

The drugs -- known as anti-retrovirals -- prevent HIV-infected cells from reproducing themselves by disrupting the necessary chemical processes. Patients take a combination of the drugs, hence the "cocktail" nickname.

But these AIDS drugs aren't perfect. Many patients don't follow the strict regimen that requires taking the medications at specific times, and the drugs cause side effects that can be debilitating.

Worst of all, the AIDS virus is rapidly developing resistance to the drugs by mutating into forms that can't be vanquished.

"The virus is getting smarter than the drugs we have for it. That happens in individuals and groups," says Michael Allerton, HIV operations policy leader for Kaiser Permanente Health Plan doctors in Northern California.

Some doctors fear that a "superbug" AIDS virus will emerge that's immune to all the existing drugs, virtually granting a death sentence to those who are infected.

Much of the current research into new treatments is focused on so-called "entry-blocker" drugs known as fusion inhibitors. They are very different from anything that's been available before, Allerton says.

"Every drug on the market that fights HIV requires infection to occur. They stop replication once cells are infected and start reproducing," he says.

But the fusion inhibitors prevent the virus from attaching -- "fusing" -- to a cell. One type of fusion inhibitor, called T-20 or enfuvirtide, is in the later stages of testing, Allerton says.

Together with existing medications and other drugs in development, fusion inhibitors should help doctors attack the virus at many levels, Douek says.

"You look at the life cycle of the virus from start to finish, from entry (into the cell) to exit, and try to target every single point," he says. "The more points you target, the more successful you are at inhibiting new rounds of virus replication and infection of other cells."

To accomplish this multi-pronged strategy, the new drugs will probably be prescribed with existing medications, Douek says. "I doubt any of them would be used on their own," he adds.

Like current AIDS drugs, the fusion inhibitors won't be trouble free, cautions Dr. Daniel R. Kuritzkes, director of AIDS research at Brigham and Women's Hospital in Boston. They can't be taken in pill form, and must be injected instead.

"That makes their administration more cumbersome," he says.

Also, the drugs will be difficult to produce and will therefore be expensive, meaning they'll probably be reserved to treat those "who have failed other therapies before," he says.

Even if the drugs do come to market later this decade, it may take additional time for them to be accepted by the medical community, Allerton says.

"Most doctors say when a new drug comes through, wait a year before prescribing it to any of your patients. And if it's a family member, wait five," he says. "It doesn't hurt for people to be aware of that dynamic."

What To Do

To learn more about HIV/AIDS and treatments, visit the Centers for Disease Control and Prevention or the National Institute of Allergy and Infectious Diseases.

SOURCES: Daniel Douek, M.D., Ph.D., chief of human immunology section, Vaccine Research Center, National Institutes of Health, Bethesda, Md.; Daniel R. Kuritzkes, M.D., director of AIDS research, Brigham & Women's Hospital, Harvard Medical School, Boston; Michael Allerton, M.S., HIV operations policy leader, Kaiser Permanente Health Plan, Oakland, Calif.
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