HIV's progressive damage to brain studied

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 have 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 a 15 percent tissue loss in the centers that regulate movement and coordination, as well as a thinning of the language and reasoning centers.

"As people are living longer, the major risk of HIV is not the immune system anymore but the brain," said Dr. Paul Thompson, professor of neurology at the University of California, Los Angeles and author of the brain scan study. "People who are doing well with HIV, living with it for over 10 years, have this progressive damage going on in the brain, well before symptoms are obvious."

For the more than 1 million Americans living with HIV, the virus that causes AIDS, it could mean minor problems with forgetfulness -- or that 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 multidrug 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.

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 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.

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 percent of the patients now on combination drug therapy have developed dementia.

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 protect 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 the University of California, San Diego.