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|November 7, 2005||E-mail story Print Most E-mailed Change text size|
Scans show loss of brain tissue with HIV
Neurologists who study AIDS have watched, waited and worried for nearly a decade about the long-term effect of HIV on the brain. They've known that the drug cocktails that so effectively extend lives don't protect the brain very well from the virus.
Now they've gotten their first actual look at the destruction HIV causes in living brains. A study published by the National Academy of Sciences last month used 3-D brain scans to see how much tissue was damaged. In vivid, color-coded images, researchers found up to 15% tissue loss in the centers that regulate movement and coordination, as well as a thinning of the language and reasoning centers.
For the more than 1 million Americans living with HIV, the virus that causes AIDS, it could mean minor problems with forgetfulness — or it could mean early-onset dementia is on the horizon.
The study compared 26 infected people on treatment — none of whom showed symptoms of dementia — with 14 HIV-negative people. The brain deterioration seen among those with AIDS could cause slowed reflexes, mild vocabulary loss or poor judgment.
There just isn't enough experience with the multi-drug treatment, available only since 1996, to predict whether symptoms will stabilize or worsen.
It's long been understood that the drugs that keep HIV in check, like many other medicines, don't get to the brain in the same way they get to other organs. That's because blood vessels in the brain are less permeable than those elsewhere in the body and have an additional coating to prevent blood leakage into brain cells.
"It's as though you have a tight pipe, and then insulate it more," said Dr. David Clifford, head of the Neurologic AIDS Research Consortium at Washington University School of Medicine in St. Louis. The biological design, called the blood-brain barrier, is nature's way of protecting the brain. But it also acts to make it more difficult, though not impossible, for helpful drugs to get in. The brain ends up being a sort of sanctuary for HIV.
"The biggest concern is that this is the tip of the iceberg," said Clifford, who has been involved in AIDS research since the epidemic emerged in 1981.
The ability to treat AIDS at all was a tremendous breakthrough, perhaps pushing some of the drugs' limitations to the back burner of research. "The issue of cognitive problems in AIDS has kind of been overlooked," says Dr. Elyse Singer, a neurology professor at UCLA. "It has become a passť issue in the past couple of years. The drugs make people better, and you don't have horribly demented people doing crazy things any more."
But that doesn't mean that no damage is being done. "We should not be complacent about the brain in HIV," Clifford said.
Since 1996, many in the developed world have grown complacent about AIDS in general. That's when everything about the epidemic changed. Treatment known as highly active antiretroviral therapy was approved, and today, AIDS drugs are taken in combinations, often dozens of pills each day. They're expensive, costing $1,000 to $2,000 a month. They have troubling side effects including annoyances such as nail fungus and chapped lips, and real concerns such as increased risk of heart disease, stroke, diabetes and osteoporosis. And the drug regimen demands perfect compliance to keep working.
But for most people, the therapy worked. So seemingly overnight, the relentless death march of AIDS slowed down.
Before drug cocktails were available, two-thirds of AIDS patients suffered severe dementia at the end of their lives, Clifford said. Within six months, they'd go from losing focus to increased forgetfulness to a loss of interest in reading or even watching TV. As brain damage quickly worsened, by the end of their lives, they were incontinent, immobile and vegetative.
Right now, AIDS dementia is rare, said Dr. Mark Katz, regional HIV physician coordinator for Kaiser Permanente of Southern California. Only about 5% of the patients currently on combination drug therapy have developed dementia.
"I take care of 250 patients," Katz said. "I have many patients with some mood alterations. But I can't remember the last case of true dementia that I've seen."
And yet the brain remains vulnerable to this virulent and unpredictable virus.
In addition to the brain scan report, the National Institute of Mental Health has funded a long-term study of brain function in people with HIV that will eventually enroll about 1,600 people and watch them over time. "Our initial findings are suggesting that, indeed, the population isn't performing normally," says Clifford. "About 50% have subnormal performance."
They might be slower on computer keyboards, working crossword puzzles or have difficulty keeping track of what's been said in a conversation. They may even begin to move more slowly.
That could well describe Michael Sausser, 44, of Van Nuys. He believes he's been infected with HIV since 1988. As a city planner, he was used to keeping phone numbers, schedules, names and deadlines in his head. Then in 1994, he found that he couldn't remember which numbers to dial. He forgot appointments. He missed deadlines.
At the worst of it, he lost his job and his judgment became so bad he got into legal trouble. "I was arrested for keying cars," he says. "Anybody with half a brain wouldn't have done it. It was totally out of character. I didn't have a brain for consequences."
In the nick of time, combination therapy was approved and Sausser began treatment. His symptoms eased, a likely indication that drugs had an effect on his brain. But he's still left with some permanent brain cell loss.
He has problems with short-term memory, forgets if he's added both the flour and sugar when he's baking, and has trouble stringing words together for anything longer than a simple sentence.
"They're not necessarily the kinds of things that people notice, but they create big problems in my life," he says.
No one yet knows how great a problem looms. It could be that lowering the amount of virus in the rest of the body, as combination therapy does, will go a long way in protecting the brain, despite the blood-brain barrier.
But even mild to moderate problems among a significant proportion of those infected with HIV can be a public health issue. "Because people are living longer, we're seeing a slow growth in the number of people who have [cognitive problems]," says Dr. Igor Grant, director of the neurobehavioral research center at UC San Diego.
It's been only 24 years since the puzzling occurrence of unusual cancers and infections were identified as AIDS, and just less than 10 years since effective treatment became available. What will happen to the brains of people on treatment is one of the mysteries of this unfolding epidemic.
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