That large-scale study, called CHARTER (for central-nervous-system HIV antiretroviral therapy-effects research), began in 2002 and received $38 million in NIH grants to follow 1,500 patients. According to Igor Grant, a University of California, San Diego, neurologist who heads the effort, motor skills are often impaired as well. Some patients develop a tremor or experience difficulty with balance. Some experience seizures, and others appear to undergo fundamental character changes, not uncommon in brain injuries. “I have many patients who say their personalities have changed, or their partners say, ‘He’s nicer,’ or ‘He’s meaner,’ ” says Anthony Geraci, an HIV neurologist in Manhattan. Some even develop interests in areas that had never fascinated them in the past, he says. “Certain parts of their brain will be released, if you will, and they start being able to do things they couldn’t do before.”
There’s significant controversy over these findings. Because the deficits can be relatively minor, many patients have had trouble convincing friends and family—even their own doctors—that they’re experiencing significant symptoms. “This is largely unnoticeable for most people, in my impression,” says Judith Rabkin, a researcher at the New York State Psychiatric Institute and Columbia University’s psychiatry department. As a specialist in HIV-related psychiatric issues, she treats hundreds of patients with these issues, many of whom are poor and have other reasons to complain of dementia, like long histories of substance abuse or co-infection with hepatitis C. But unless they have relatively complex jobs, the deficits may not ever cause problems, she says. “Up to 80 percent of our patients you could classify as impaired, but it doesn’t impact their everyday lives.” (In a related criticism, the activist Mike Barr wonders what sort of HIV patients are enrolling in these neuropsychology studies. “From my perspective, ‘normal’ HIV-positive folks either are unwilling to enter in these sorts of studies, are not attracted by the customary financial incentives to participate, or are simply happy/satisfied with the care they are getting from their HIV specialist,” he wrote to me in an e-mail.)
For the problems with dementia, most researchers blame HIV itself, which it turns out can continue replicating in, and damaging, the brain despite being controlled in the bloodstream. Dr. Scott Letendre from the University of California, San Diego, tested spinal-fluid samples from patients who had undetectable levels of virus in their blood. Over a quarter of them tested positive for viral activity in the fluid that surrounds the brain. It turns out that some drug combinations are not as good as others in penetrating the blood-brain barrier. This finding sounded an alarm for AIDS doctors to pay closer attention when prescribing.
But in many cases of dementia, there are no signs of viral activity around the brain, suggesting other factors may be at play. At the Manhattan HIV Brain Bank at Mount Sinai, researchers have dissected the skull contents of 250 volunteers who agreed to a series of psychological interviews and neurological exams, then promised to hand over their brains at death. (One is the gift of Fred Gormley, a felicitous writer who toiled with me years ago at the now-defunct New York Native; he wrote about his life as a brain donor before his death from AIDS complications in 2002.) According to Dr. Susan Morgello, who directs the lab, most people who showed signs of dementia while alive do not have evidence of HIV in their autopsied brain. What they do have in common, she says, is evidence of persistent inflammation, which alone could account for the cognitive damage.
But Morgello is investigating something that’s both more surprising and less so: The inflammation might be caused as much by the patient’s emotional and psychiatric burden as the virus’s pathological course. “We have screamingly high rates of major depressive disorders, substance abuse and dependency, and post-traumatic-stress disorder,” she says of the Brain Bank donors. “About 40 percent of our patients have major depressive disorders when they come to the study. Substance abuse and dependency, that’s a continually moving target, but when we run urine toxicologies, about 30 percent contain illicit substances,” she says. These multiple “insults to the brain” are enough to cause the entire upswing in dementias, she says. But she admits she’s only speculating. “I wouldn’t even say we have 50 percent of the answer here,” she says.
Whatever the cause, if left unchecked, the inflammation can destroy brain tissue. Some MRI studies show atrophy of the gray matter in areas that render a person unable to concentrate on reading or remember simple facts. This might account for the case of a 44-year-old man I met recently, a wild overachiever in his career (scientific research) who decided recently to return to school for an advanced degree. To his shock, he flunked his first semester. “I couldn’t memorize the subjects,” he says. He also began having trouble remembering the names of old friends and colleagues, struggling to find words and understand conversations, and keeping track of procedures at work. Increasingly, he has a sensation of floating above the tableaux of his own life. “I started to be like a zombie. Like I’m there with my friends, but I’m not there,” he says. “And I started to think, Oh my God, I’m becoming stupid, you know?” Doctors have diagnosed mild HIV-related cognitive disorder.