Experts Offer Advice on Managing HIV Neurocognitive Impairment

Since effective antiretroviral therapy (ART) for HIV-infected people was introduced in 1996, some remarkable things have happened.

Life expectancy at age 20 increased from nine years in the period 1993-1995 to 24 years in 2002-2004, several years after ART became a routine part of treatment for HIV-infected individuals. Deaths due to HIV/AIDS-related causes decreased from 3.79 per 100 person-years in 1996 to 0.32 per 100 person-years in 2004. Some individuals who were on the verge of death from AIDS and who were treated with ART managed to rebound and are still alive 15 years later. People who are newly infected with HIV may even be capable of achieving a normal lifespan if they rigorously adhere to ART treatment and can tolerate the unpleasant and sometimes pernicious side effects it can produce.

Credit: Felix Möckel/istockphoto

In addition, once clinicians started to vigorously treat HIV-infected patients with ART early in their illness, the incidence rate of HIV-related dementia, which was previously between 10 percent and 20 percent, dropped to between 3 percent and 5 percent.

But the fight against the disease's ravages is not over.

Even in this era of ART treatment, about half of HIV-infected patients will experience mild to moderate neurocognitive impairment, a large national study published in the December 2010 Neurology indicated.

Two HIV experts—Justin McArthur, M.D., of Johns Hopkins University and Bruce Brew, M.D., of St. Vincent's Hospital in Darlinghurst, Australia—referred to this prevalence of neurocognitive impairment in ART users as a "hidden epidemic" in the June 1, 2010, issue of AIDS.

Another HIV expert, psychiatrist Karl Goodkin, M.D., Ph.D., concurred during a recent interview. "Psychiatrists, neurologists, infectious disease specialists, and primary care physicians are not as aware of this epidemic as they should be." Goodkin is director of Mental Health Services at the AIDS Healthcare Foundation, the nation's largest provider of HIV/AIDS medical care, and director of clinical research, psychiatry, and behavioral neurosciences at Cedars-Sinai Medical Center in Los Angeles.

However, ART users who are afflicted with neurocognitive problems are certainly aware of how serious these problems are, Marshall Forstein, M.D., an associate professor of psychiatry at Harvard Medical School and another HIV authority, said. "Unlike the kind of cognitive disorders we see with, say, Alzheimer's or multiinfarct dementia, which are diseases of the cortical structures of the brain, HIV tends to initially infect the subcortical areas of the brain that have less to do with intellect and more to do with the management of information and the processing of information and the use of memory for doing things—including what we call ‘working memory,’" he explained. "So people are acutely aware of these losses. For instance, it could be difficulty in handling finances or in preparing meals. It could be impairment in driving. It could be problems at work."

Francisco Fernandez, M.D., of psychiatry at the University of South Florida and also an HIV expert, said that he would rate the neurocognitive impairments that ART users experience as just as burdensome as the depressive spectrum disorders that they also often experience. "They are different because their features are different, but in terms of human suffering, both can cause an enormous amount of despair and dysfunction."

Detailed Psychiatric Assessment Crucial

Nonetheless, psychiatrists or other clinicians can help ART users with their neurocognitive problems, these HIV experts agreed.

"The first thing is to make sure that there is no other cause," said Forstein. "This could be depression, endocrine dysfunction, Alzheimer's disease, multiinfarct dementia, toxic reaction to medications, substance abuse."

Actually, if there were only one thing that psychiatrists could do to lessen neurocognitive impairments in ART users, Fernandez said, it would be to "make an accurate assessment... and support it with neuropsychological testing."

"You then need to look at the ART regimen patients are on and see whether it includes ART medications that penetrate the brain best," Forstein said. "If not, then a change in regimen, or perhaps an addition to it, may be in order."

"Unfortunately, the protease inhibitors—the ART drugs that have dramatically reduced HIV morbidity and mortality—do not penetrate the brain well," Goodkin noted.

"Psychostimulants may also help goose the brain so that it can function better," Forstein pointed out. "There is a lot of information that they work well in men, women, children, and adolescents infected with HIV, and while they don't restore them to their previous levels of performance, they do improve function."

Other Treatments Being Explored

Meanwhile, other treatments for neurocognitive impairments in ART users are being explored, these HIV experts noted.

For example, "It looks as if it is more than just HIV in the brain that accounts for the damage that we are seeing; inflammation resulting from the brain's immunological system trying to fight off the HIV virus may be responsible as well," Forstein explained. "Thus for people who are having a lot of inflammation, even in the absence of a lot of viral replication, there may be a significant loss in cognitive function. This situation suggests that agents that counter inflammation in the brain might also counter HIV-inflicted brain impairment."

Giving patients a neuro-anti-inflammatory agent as soon as they are diagnosed with HIV, that is, while still asymptomatic, might muffle the brain's immune response to HIV and prevent loss in cognitive function, Forstein speculated.

"But a lot more research needs to be conducted to find medications that can counter neurocognitive impairment in ART users," Goodkin emphasized. "We need research not just on the psychostimulants and anti-inflammatory agents, but also on dopaminergic agonists and the SSRIs since decreased dopamine and decreased serotonin have been detected in the cerebrospinal fluid of such patients. Their neurotrophic and anti-inflammatory effects are another reason to try the SSRIs in HIV patients with neurocognitive impairment."

What Will Next Decade Bring?

"I think the next 10 years are going to be about testing people with HIV sooner, starting ART medications in people infected with HIV sooner, and trying, in HIV-infected people, immune modulators, psychostimulants, and antiretrovirals that penetrate the brain and are actually effective against the virus there," Forstein said. "I think we need a multipronged attack. We are talking about potentially more than a couple of million Americans who will become cognitively impaired to the point of having to go onto disability if progress against HIV-induced cognitive impairment isn't made."

And the need for major advances to combat HIV-related neurocognitive impairment will be particularly pressing with the aging of the American population, Fernandez stressed, since "there is an overlap between the neuroinflammatory process of HIV and the neuroinflammatory process of Alzheimer's disease."

More information about HIV neuropsychiatry is available from the APA Office of HIV Psychiatry at (703) 907-8668.