Transcript: HIV and the Brain

May 11, 2009

At the 16th Conference on Retroviruses and Opportunistic Infections (CROI) in Montreal, David Evans talks with Scott Letendre, MD, from the University of California in San Diego, about the latest research on HIV and neurocognitive functioning. Dr. Letendre reveals how commonplace cognitive disorders are in people with HIV, and what you and your doctor can do about them. To view the video click here.

David Evans: Welcome. This is David Evans from AIDS Meds and POZ. I’m here with Dr. Scott Letendre. He is an associate professor of medicine at the University of California at San Diego. Welcome, Doctor Letendre.

Scott Letendre: Thank you.

DE:  Thank you. We’re here to talk about neurocognitive problems in HIV. And I’m wondering if you can sort of succinctly describe what we mean when we talk about neurocognitive decline?

SL: Sure. So the definitions for cognitive decline, or what we’re now calling HIV-associated neurocognitive disorders, were revised just a couple of years ago. And there are four basic elements. One is that the cognitive problems that someone is having did not exist before they had HIV. The second is that they are not very ill with something like a drug intoxication or adverse event of a prescribed medication or a severe infection, so they don’t have what we call delirium. The third is that they are impaired in at least two cognitive abilities. And what we mean by cognitive abilities are things like they have difficulty learning new information, they have difficulty remembering information they previously learned, they have problems with their motor function and other cognitive abilities.  And then the fourth is that they have problems with activities of daily living. And so that’s particularly a problem with two of the three sub disorders that we call mild neurocognitive disorder and HIV-associated dementia.  

DE: Do we have a sense for the magnitude of the problem or are we starting to get a sense for the magnitude?  

SL: Well, one of the nice things at this conference is that there are a few studies that are confirming what others have reported in the past. So I work with the charter study, and there’s a site of charter in New York, and the charter study has found that of the 1600 people in the study about 53 percent have worse neuropsychological performance than would be predicted compared with healthy controls.

DE: Oh, wow.
 
SL: And other studies like the Sigma Study have found similar numbers; between about 40-50 percent of people don’t seem to be performing as well as we would expect based on healthy people.

DE:  Have we gotten to a point do you think where the average person’s HIV physician is actively looking for this, or is it the kind of thing you can or should actively look for?

SL: Well, there’s been a shift in the last few years. So I’d say a few years ago what we heard predominantly was that this wasn’t a problem in clinic. That the severe sort of dementia that was more common back in the 90s was not being seen as much and therefore it wasn’t a problem.  But as the information has accumulated that even mild and moderate cognitive impairment can interfere with someone’s ability to take their medications and to perform their jobs and to even live as long as people who do not have cognitive impairment, I think clinicians and patients have begun to become more interested in this. And so I think more clinicians are looking for it now than were before, but there is still I think a lot of progress to be made in terms of how systematically it’s looked for in the clinic, and how many clinics are truly looking for it on a regular basis.    

DE: Is it the kind of thing where if someone felt that they themselves were beginning to have difficulty with memory, concentration, thinking, and learning, would they seek a referral to a neurologist typically, or is this something their physician can diagnose in the office?

SL: Like a lot of things, a primary care provider can do a lot before needing to refer someone.  And that’s particularly important in less urban areas where there isn’t a large referral network.  

DE: Sure.

SL: And so many primary care clinicians can do quite a lot in terms of creating a patient questionnaire that people can complete in the waiting room while they’re waiting to see their physician. In terms of doing a brief screening, there are several brief screening tests that are imperfect but they’re at least good enough to maybe detect a possible problem so that more testing can be done. And then talking with someone’s family, and doing a brief physical exam and doing some brief blood tests. All those things can be done without a referral, and can provide some information about whether someone might have a problem that needs further investigation.

DE:  You know there seems to be more of an emphasis in the last year on the role of age in a lot of aspects of HIV disease. And I’m wondering what impact does age have in this regard on cognitive function?

SL: Well, a few years ago an investigator named Victor Valcour from the University of Hawaii had assembled an aging cohort, and to be considered having older age, the criterion was not very stringent, it was only older than 45 I think.

DE: (Laughter) There are some people who would be disturbed with that criterion.

SL: Including me.   And he compared them to people who I think were younger than 40. And Victor found a difference between those people who were older in terms of what proportion of them were cognitively impaired and the people who were younger. There was one or two other studies, but since then others have confirmed those findings. And I think as our population of people with HIV is growing older, even into their 40s and their 50s, what we’re seeing is that the risk of developing cognitive impairment is much greater. And there are many ideas about what that might be due to. It might be due to how long someone has lived with HIV, it might be due to early aging changes that would have occurred had someone lived without HIV into their 60s or 70s, and it could be due to incomplete treatment to the brain with antiviral therapy and other explanations.  

DE: There are a growing number of people who are now aging into their 50s and 60s with HIV. A lot of them have been on antiretroviral drugs for a long time, have been positive for a long time and have problems with their cholesterol, seeing metabolic changes as we call them, some have developed Type 11 diabetes; does that have any influence on cognitive function?

SL:  Yeah, so some of the other findings at this conference have been comparisons between cognitive impairment and elements of metabolic disorders, whether it’s hyperlipidemia, high levels of cholesterol in your blood, insulin resistance or higher levels of glucose or sugar in your blood than you should have, or frank diabetes, elevated blood pressure, hypertension and others.  And so there were several reports comparing those factors to cognitive impairment and finding associations. So in the past there have been a study or two finding that people with insulin resistance, having borderline elevated sugars in their blood, was associated with a higher risk for cognitive impairment. And at this meeting Allen McCutcheon from our charter group reported that we did not find an association with insulin resistance or with having higher levels of glucose in the blood, but he did find a strong association between having diabetes and having cognitive impairment.  So to the extent that some antiretrovirals may cause or make that worse, or to the extent that HIV disease causes that, that may be putting people at increased risk for brain injury.   

DE: You know our readers and viewers are often eager to know what they might be able to do to either avoid or prevent something from occurring. I know sometimes HIV can lag behind what we learn in the general population, but have we learned of things over the years that may help be more protective against cognitive decline in terms of things that people can do?

SL: Well, I would say the first thing is to be aware, which is why what you’re doing is so very important, is to increase awareness and educate people about the condition so that they can hopefully detect it early, tell their provider early and get treated and hopefully have full reversal back to normal function. So I think education and awareness is very important. There have been several studies. In San Diego we have a big problem with methamphetamine use and other stimulants like cocaine also seem to injure the brain, so if someone has continued to use methamphetamine or cocaine, that would be something else they can do to protect their brain. They don’t have to use it all the time; even intermittent use seems to cause cognitive problems that can be durable. And then if someone is going to be starting an antiretroviral regimen and they are having cognitive problems, then choosing a regimen that has better penetration into the nervous system may be important.

DE: Okay, okay. And we have a fairly good sense of what those anti-retrovirals generally are, so if someone were to look online and look for that kind of thing, they would be able to find information on which penetrate into the central nervous system?

SL: More and more.  You know, looking back at all the studies that have been done, the definitions that were used to identify which drugs were better penetrating and which drugs were not, varied. And what we’ve seen over the last few years is more consistency, and as that’s occurred there has been more consistency in the findings that the antiretrovirals that penetrate into the brain better, better reduce HIV there, and in some studies seem to also improve cognition. So yes, there is more data about that, and yes, someone should be able to find information about that on the Internet. But I’m also happy to answer emails if someone wanted to inquire about that.


DE: Fantastic. Well, thank you so much for taking the time.

SL: Alright. Nice to meet you.   

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