Another Kind of AIDS Crisis

Left: Russell Steinke. Age: 56 / HIV: 23 years / Has suffered from: memory loss, nerve damage in feet, lipodystrophy, fatigue.
Right: Enrico McLane. Age: 52 / HIV: 17 years / Has suffered from: short-term memory loss, two hip replacements.
Photo: Marco Grob

When David Simpson was working at Mount Sinai Medical Center as a young neurologist in 1984, the neuro-AIDS program occupied a dark warren of tiny rooms in the complex’s basement. It was a place overwhelmed by plague, a final stop on a doomed journey. “People came in with seizures or paralyzed on half their body. People came in in comas. Men were screaming—I have videotapes of this,” says Simpson, the program’s director. “Bedbound, incontinent, couldn’t sleep. They could be dead in a number of days.”

Those are memories of a distant past. When the drugs arrived in 1996, they ended this kind of pitiless death and put many AIDS wards out of business. The famous St. Vincent’s seventh-floor ward now houses offices for the orthopedic department. The sixth floor at New York Downtown, the eleventh floor at Beth Israel, the seventeenth floor at New York-Cornell, whole wings at Lenox Hill, Bellevue, and Harlem hospitals—those dire corridors where, in a little over ten years, more than 60,000 New Yorkers drew their last painful breaths—have been cleared out and repurposed. “So much trauma, there was so much history,” says Victoria Sharp, who directed AIDS programs at Beth Israel, St. Clare’s, and St. Luke’s-Roosevelt, “and they’re gone.” Simpson stayed in business by expanding into other areas of neurological research (using Botox to help treat stroke paralysis, for one).

But in the last year or so, doctors have been troubled by the emergence of a new kind of AIDS story. Take the case of James L., 46. After testing positive in 2001, he went on a drug cocktail and life returned to normal with little effort. His exercise regime only intensified. He even went back to school for a master’s degree. At work, he rose to a six-figure position at a telecommunications firm, and his personal life flourished. He was, he told me, “a regular gay male.”

Then, halfway through a screening of the film Syriana in his local cinema, he had a disturbing revelation. “He sat through about half the movie before he realized suddenly that he had seen the same movie two weeks earlier,” says Simpson. Indeed, James ultimately pieced together evidence suggesting he’d seen the film on three separate occasions. The same problem haunted him at work. Where he had once earned praise for his organizational skills, he now drew warnings. He seemed incapable of recalling recent events with any reliability. “It’s an Alzheimer’s-like state,” he explains. Earlier this year, Simpson diagnosed him with HIV-associated cognitive motor disorder.

James is on medical disability today, acutely aware of what he is missing. “I want more out of life,” he told me one afternoon recently. “I spent a lot of money on my education, and this barrier might keep me from enjoying my fifties and sixties. But I’m much more concerned about my financials than my own health at the moment. People like me in the business world? I don’t believe they go together well.”

Some fifteen years into the era of protease inhibitors and drug cocktails, doctors are realizing that the miracles the drugs promised are not necessarily a lasting solution to the disease. Most news accounts today call HIV a chronic, manageable disease. But patients who contracted the virus just a few years back are showing signs of what’s being called premature or accelerated aging. Early senility turns out to be an increasingly common problem, though not nearly as extreme as James’s in every case. One large-scale multi-city study released its latest findings this summer that over half of the HIV-positive population is suffering some form of cognitive impairment. Doctors are also reporting a constellation of ailments in middle-aged patients that are more typically seen at geriatric practices, in patients 80 and older. They range from bone loss to organ failure to arthritis. Making matters worse, HIV patients are registering higher rates of insulin resistance and cholesterol imbalances, and they suffer elevated rates of melanoma and kidney cancers and seven times the rate of other non-HIV-related cancers.

Whether this is a result of the drugs or the disease itself, or some combination, is still an open question and certainly varies from patient to patient and condition to condition. Either way, it is now clear that even patients who respond well to medications by today’s standards are not out of the woods. Current life-expectancy charts show that people on HIV medications could live twenty fewer years on average than the general population. “It’s spooky,” says Mark Harrington, who heads Treatment Action Group, a New York–based HIV think tank. “It seems like the virus keeps finding new tricks to throw at us, and we’re just all left behind going, What’s going on?

Left: Norma Martinez. Age: 61 / HIV: 12 years / Has suffered from: lipodystrophy, fatigue.
Right: Michael Davis. Age: 47 / HIV: 28 years / Has suffered from: lipodystrophy, dysplasia, Crohn's disease.
Photo: Marco Grob

It might seem churlish to complain about the consequences of aging with HIV, when, for the first six years of the plague, survival itself was at stake. Back then, life expectancy after a first doctor’s visit was eighteen months. Tears of relief greeted AZT, a toxic old cancer drug that was reintroduced as an AIDS treatment in 1987. Researchers hoped AZT would neutralize the virus before it had a chance to cause infection. But even at doses so toxic that the drug destroyed livers and caused severe muscle loss, it proved no match for the virus’s ability to mutate. For almost fifteen years, no real hope crossed the horizon until researchers identified a promising new class of drugs. Called protease inhibitors, the pills attack cells that HIV has already infected, blocking the enzyme they use to replicate. In studies, the drugs still proved vulnerable to mutations. However, when taken in combination with the older drugs (including AZT), that vulnerability seemed to nearly vanish. What’s more, the drug cocktails somehow magnified the power of each individual drug to the point where together they could push the level of circulating virus down below the ability of sensitive tests to detect. Even more thrilling, it became clear that with the virus suppressed, the body could actually reconstitute its immune system. In most patients on successful therapy (especially those who didn’t delay or interrupt treatment), T-cell counts return to near-normal levels. Practically overnight, the number of people who developed opportunistic infections like pneumonia and Kaposi’s sarcoma dropped 70 percent.

What wasn’t clear at the time was how long patients would be expected to take these drugs. Initially, Dr. David Ho of the Aaron Diamond AIDS Research Center predicted it would be just a few years—he famously speculated that the drugs might eventually clear HIV from the system. This proved to be fantasy. We now know that HIV finds hiding places in the body out of the drugs’ reach. Once medication is halted, these sleeper cells send out armies of new viral invaders to resume the war undaunted. So the current thinking is that the drug regimens are lifelong commitments.

As a consequence, researchers fiercely debate at what point in a patient’s illness to begin prescribing them. The initial theory was an approach called “Hit early, hit hard,” meaning everyone with HIV should be on full-dose combination therapy, even those without symptoms. Alarmed by the toxic exposure, some experts began arguing to hit a little later. Federal standards were adopted that recommended the drugs to people with CD4+ T-cells under 500, a near-normal count, then were revised to 350, then 200.

“You realizeyou can’t read and you used to read, says a former Balanchine dancer. “That’s the hardest part, when you cognitively know you’re losing yourself.”

But now a number of studies suggest that people whose CD4s are allowed to drop that low are destined to poorer outcomes. At an AIDS conference earlier this year, researchers from Seattle presented a large-scale study that compared patients who started treatment early with those who waited. They found delaying therapy boosted the odds of dying by either 69 percent or 94 percent over a decade, depending on how low the patient’s T-cell count was. These are staggering numbers. Though the investigators say that randomized long-term studies are needed to confirm their work, they nonetheless propose beginning treatment earlier. Leading AIDS doctors are persuaded. “Many of us who see large numbers of HIV patients are becoming superaggressive,” says Dr. Stephen Dillon, who practices in the West Village. “I don’t believe everybody needs to be started on meds. But I do believe that we need to start earlier than we have been for the last five to ten years.”

In a dramatic move last week, the National Institute of Allergy and Infectious Diseases upped the ante even further by announcing a massive new plan to test virtually every single adult in the Bronx and the District of Columbia—homes to some of the highest rates of infection in the country—and put everybody who tests positive on anti-HIV drugs, whether they have depleted T-cell counts or not. Dr. Anthony Fauci, the nation’s top AIDS official, said the main goal of the program was to stem transmission of the virus. Untreated patients are extremely infectious. Effective treatment suppresses HIV to such a degree that transmission risks can be virtually eliminated.

Still, the proposal is fraught with ethical peril. Because of the stigma associated with HIV infection, advocates have long insisted that testing for HIV should only be done in combination with extensive counseling. In addition, a number of leading researchers have called for more research on the drugs’ side-effects before putting more people on them, according to Jeffrey Laurence, a professor of medicine at Weill Cornell Medical College in New York. For one thing, he says doctors wonder if African Americans fare worse on the drugs than whites. “Our chairman of medicine said he’s never seen a white person with HIV and kidney disease, it basically doesn’t happen. There’s a whole bunch of information we need before pushing forward with this.”

Left: Cesar Figueroa. Age: 50 / HIV: 20 years / Has suffered from: dementia, neuropathy, depression
Right: Mike Weyand. Age: 58 / HIV: 20 years / Has suffered from: osteoporosis, lipodystrophy, memory loss.
Photo: Marco Grob

That’s a position advocated by many activists. Dr. Joseph Sonnabend, the founding force behind AMFAR and a number of other agencies, is especially incensed by a proposal, currently under consideration by the Centers for Disease Control and Prevention, to make the drugs available to people who are HIV-negative on the theory that they will help prevent transmission. “It’s all quite bizarre, and I wonder what is driving it,” he wrote in an e-mail from his London home.

It is true that the clinical picture of life with treated HIV disease is only now beginning to come into focus. A study presented at a conference in February in Montreal showed that otherwise healthy people on HIV medications at about 56 years of age had immune systems comparable to HIV-negative subjects whose median age is 88. Perhaps as a result, many diseases that typically attack the very old are striking younger HIV-positive people disproportionately, like diseases of the liver, kidney, heart, and veins. One study found that 55-year-olds who are HIV-positive have all the telltale signs of late-life frailty—muscle loss, fatigue, and rheumatological disorders.

The newest data show that middle-aged patients have dramatically increased rates of bone loss and fractures for their age. Some 60 percent of HIV-positive men in their forties have osteoporosis or its predecessor condition, a problem that typically isn’t diagnosed in men until well into their eighties. Jules Levin, founder and executive director of the New York–based National AIDS Treatment Advocacy Project, only found out about this two years ago, when he stumbled and shattered his wrist. He was 57 at the time and in exceptionally good shape, other than his undiagnosed osteoporosis. “This is what opened my eyes to all of this stuff,” he says. “Aging is the No. 1 problem in HIV today.”

Researchers are convinced that bone loss, perhaps more clearly than the other conditions, is a direct side effect of the medications, while the brain issues are more likely to be related to HIV itself. Further puzzling to researchers is why some patients don’t experience any problems at all, even after living with HIV for decades. Dr. Justin McArthur at Johns Hopkins says genetic factors may be at play. That might explain the case of two Brooklyn-based neuroscientists I met recently, both of whom tested positive 22 years ago, a few months after they started dating. They asked me to call them by their middle names. Joseph has had almost no bumps in the road. But Donald’s path through HIV has been extremely tumultuous. Though his body responded well to the drugs, over the years he has nonetheless developed AIDS-related pneumonias, skin cancer, seizures, heart problems, and systemic infections ordinary patients might have rebuffed. He managed to keep a high-powered career in research and even returned to school to study law recently. But with weeks left before getting his law degree this summer, he developed a case of HIV encephalitis that left him in a state of disorientation. During a recent visit to their home, he was unsteady on his feet and sometimes unable to answer simple questions.

“Do you know what today’s date is?” his husband asked.

Donald looked at him blankly, then gave a small, nervous laugh.

Joseph tried another tack. “What year is it?”

“That, I got this morning,” Donald answered quickly. Maybe so, but now it wasn’t so easy. He glanced at the corners of the ceiling. It finally came to him. “Two thousand and nine,” he said. “Because I was supposed to graduate this year.”

It was hard to imagine, but just weeks earlier this man was about to earn a law degree. I asked him, “Have you lost your legal education? Is that still there?”

He smiled. “Get back to me on that one,” he said. Then tears brimmed his eyes, and he let on for the first time that, like the character in Flowers for Algernon, he was a conscious witness to his own decline. “I’m fearful that I’m going to be a janitor someplace,” he said.

“He had his Ph.D. at 25,” Joseph told me. “His thesis work—it’s in nearly every new neuroscience textbook in the country.”

“True,” Donald agreed. “Now what am I doing?”

Brain impairments are the unexpected new minefield among HIV-positive people who have been on protease inhibitors. According to research presented this summer at the international AIDS conference in Cape Town, South Africa, 52 percent of all Americans infected with HIV (the mean age of which is just 43) suffer from some type of cognitive impairment—mostly mild or moderate dementias, but which nonetheless can impede one’s ability to function on a day-to-day basis. This is a staggering finding. Among people without HIV, around 10 percent of individuals under 60 experience such problems.

Left: Joe Westmoreland. Age: 53 / HIV: 27 years / Has suffered from: memory loss, fatigue, peripheral neuropathy in feet and hands.
Right: Doug Turkington. Age: 52 / HIV: 20 years / Has suffered from: osteoporosis, two hip replacements.
Photo: Marco Grob

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.

In contrast, others show deep disturbances of the white matter of their brains, the deep connective nerve tissue responsible for motor coordination and executive function—the region that allows us to make a plan and to follow through on it. A high-level executive assistant I’ll call Martina—diagnosed HIV-positive 22 years ago—tells me she has finally gone on disability recently, unable to juggle her own pared-down schedule, much less someone else’s. An MRI revealed significant changes in her white matter, which are likely irreversible—a possibility that devastates her. “I feel awful,” she says. “Lately my husband has been saying, ‘You know what? I think I need to take over the bills.’ For him to say that, I must be getting worse.”

For those trying to hold down jobs, even minor cognitive disturbances can change lives dramatically, according to experts and patients alike. And studies show patients with minor deficits have trouble remembering to take their medications, which can lead to more serious problems like drug resistance and even early death. “We’re not talking about people who look like advanced Alzheimer’s disease,” says Dr. Grant, the lead CHARTER researcher. “But nevertheless they can have an effect on everyday functioning, which can be serious.” Plus, as Dr. Simpson puts it, “it’s scary as hell.”

That describes a former Balanchine dancer named Kenn, who, though battling HIV for 25 years, had been able to remake his career several times over until recently, when he lost his ability to process information reliably. “You realize you can’t read and you used to read,” he tells me. “That’s the hardest part, when you cognitively know you’re losing yourself.” There are perhaps 145,000 people in New York living with HIV. That’s the second-highest rate in the country according to the CDC, and one of the densest AIDS subpopulations in the developed world. And as people live longer with the disease, the number gets larger every day, fueled in part by the fact that HIV is spreading here at three times the national rate. The average age is marching upward—now at 46, they’re nearly a generation older than the epidemic’s first wave. This is true across the country as well. In just a few years, half of all Americans with HIV will be 50 or over, according to projections.”

It is surprising that this is generating so little attention. Among activists, Jules Levin, from the National AIDS Treatment Advocacy Project, has been alone in calling for more resources to study aging and AIDS, while others have turned their attention—and money—to fighting the plague in Africa and elsewhere. “Issues of aging with HIV, compared to that, is like a subtitle. It has no political thrust to it at all,” Levin says. “I’m not saying we should ignore the rest of the world, but domestic AIDS has been totally neglected, because we’re sending all the money overseas.”

In the meantime, the frontline doctors I spoke to are crying out for help. “This needs urgent, comprehensive attention,” says Paul Bellman, a prominent HIV doctor in the Village who has noticed a significant increase in such patients in the past six months. One called recently to say he risked losing his demanding job because of a sudden inability to recall simple tasks. “I wish I could say, ‘I’m so glad you called me, because this is what’s causing it.’ But I don’t have the answers. Nobody does.”

HIV Patients Talk About Their Medications, Side Effects, and Symptoms

Watch the Video

Another Kind of AIDS Crisis