HIV infection has been transformed in less than 30 years from a typically fatal condition to a chronic disease patients can live with for decades.

That longevity has HIV specialists scrambling to figure out how the virus affects the aging brain and how they will differentiate between the start of Alzheimer’s disease and cognitive issues associated with HIV infection.

“I think this is one of the more pressing issues right now in geriatric neurologic HIV (medicine),” said Dr. Victor Valcour, a professor of geriatric medicine and neurology at the University of California, San Francisco Memory and Aging Center. “We really need to figure this out.”

Doctors have long recognized that individuals infected with HIV can experience mild to severe memory or cognitive decline. HIV-associated neurocognitive disorders affect some 30 to 50 percent of infected patients, even those on antiretroviral drugs.

“They still run into cognitive problems, despite people having viral loads that are completely suppressed,” said Dr. Marcel Curlin, an HIV specialist with Oregon Health & Science University.

Researchers believe that may be the effect of inflammation of the brain caused by the virus. While antiretroviral drugs are effective at keeping the virus from replicating elsewhere in the body, they may not be able to fully penetrate the blood-brain barrier that generally protects the brain from toxins.

Many researchers believe that could make individuals with HIV much more susceptible to aging-related dementia and Alzheimer’s disease, in what’s known as the two-hit hypothesis.

“Having two diseases instead of one makes you present with symptoms more frequently,” Valcour said.

Doctors have seen this phenomenon in non-HIV patients. One study based on autopsies in individuals who died after the age of 80 found that many individuals who had no cognitive issues during their lifetimes still had the physical signs of Alzheimer’s disease in their brains. For some unknown reason, their brains were resilient to the effects of the disease and they showed no symptoms.

“That’s less likely to happen when people have a second disease,” Valcour said.

Individuals who also had cerebral vascular disease, such as those who experienced a number of small strokes, were much more likely to have exhibited Alzheimer’s symptoms.

“As people with HIV age, they already have that cerebral vascular disease,” Valcour said. “If that holds true for this older population, there’s increased risk there.”

Many of these questions remain unanswered in part because HIV specialists haven’t had large numbers of older patients to study. At the height of the HIV/AIDS crisis in the 1980s and 1990s, HIV primarily affected individuals in their 20s and 30s.

“Now that lump in the snake is progressing down toward the tail,” Curlin said. “Alzheimer’s disease doesn’t show up until later, and now we’re getting people who are moving into that range.”

Today, individuals age 55 and older account for more than a quarter of the estimated 1.2 million Americans living with HIV. But the risk of Alzheimer’s begins to climb exponentially after age 65, doubling every five years. As two trends intersect, doctors may be facing a lot of HIV-positive patients with dementia.

“The good news is they’re living long enough to get Alzheimer’s,” said Dr. Scott Turner, a neurologist with Georgetown University Medical Center. “But the bad news is I’m wondering whether HIV is a risk factor for Alzheimer’s.”

Turner recently documented the case of a 71-year-old man who had been HIV positive for at least 14 years and had begun to experience memory issues. Doctors used a special imaging test to show deposits of beta amyloid in the brain, a hallmark of Alzheimer’s disease.

Turner published the case report in part to draw attention to the issue because of concern that Alzheimer’s disease could easily be overlooked.

“I’m wondering whether there are a lot of people who are misdiagnosed, who are actually being labeled as HAND but they may also have Alzheimer’s,” Turner said. “Everyone sort of assumes that if you become demented with HIV, it’s HAND and end of story.”

That could stem from the fragmented nature of HIV care. HIV specialists are primarily infectious disease doctors, who may look at the patient’s CD4 count to determine how well the immune system is working, or to check the viral load to see how much virus is in the body.

“But no testing of any cognition,” Turner said. “Even if there’s a mild memory complaint, it just takes time to do cognitive testing.”

For years, the disease was so deadly, doctors treating HIV patients had their hands full just keeping the virus at bay and overcoming resistance to the medications. But as they were able to keep patients alive with complex cocktails of different drugs, they had to expand their practice to deal with issues such as high cholesterol, hypertension and heart disease that arose from the either the HIV infection or as a side effect of the treatment.

“I think Alzheimer’s falls into that as well,” Valcour said. “I don’t think there’s been particular concern around things like Alzheimer’s disease because we were dealing with a generally young population.”

Researchers are now trying to develop protocols for distinguishing HAND from the start of Alzheimer’s. That could include using PET scans to look for amyloid plaques in the brain.

“The challenge is that it’s not terribly available to people,” Valcour said. “It’s highly expensive and it’s not FDA approved. It’s not reimbursed by Medicare. It’s not something that most people are going to be able to afford.”

There is a national study underway to test the ability of PET scans to diagnosed Alzheimer’s and to justify Medicare reimbursement. Turner said doctors who suspect their HIV patients may have Alzheimer’s could get free scans through the clinical trial.

In the meantime, doctors are left with more questions than answers.

“How are clinicians going to vet whether this is just HIV itself or whether there is an ominous second disease brewing?” Valcour asked. “I think there is a real risk for older HIV patients to be diagnosed a little bit late, because they’re living with a disease that alone can cause cognitive impairment. Doctors may not recognize the early signs.”

— Reporter: 541-633-2162, mhawryluk@bendbulletin.com

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