March 30, 2010
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Myles Helfand: Speaking of complications that tend to emerge as HIV-infected patients age, we saw a number of studies that were presented at CROI having to do with CNS [central nervous system] complications, which seems to be the issue that never dies. AIDS-related dementia was a key concern a decade or more ago. Now we're seeing a number of different signs of CNS-related problems emerging over time in HIV-infected people, despite suppressive antiretroviral therapy.
Pablo Tebas: Yeah. There were several presentations from the CHARTER cohort, which is a large cohort, around 1,500 patients in San Diego and multiple other sites in the U.S., showing that in spite of virologic control, a sizable number of patients with HIV have what they call HAND: HIV-associated [neurocognitive disorders]. This is a subtle neurocognitive impairment. You might not notice it in the activities of your daily living. And you can only ascertain it if you do some of the sophisticated tests that are done as part of these cohort studies.
So it's another one of the reasons to try to push people to think about treating HIV earlier, to try to prevent these long-term complications. We talked first about cardiovascular complications. We talked later about cancers. Now we are talking about this neurocognitive impairment.
One of the things that people have been talking a lot [about] in the last few years is, do we need to use medications that penetrate well in the spinal fluid? There was a study from England, I think it was, looking at individuals who had started antiretroviral therapy that penetrated well on the CSF [cerebrospinal fluid], versus individuals who started antiretroviral regimens that didn't penetrate that well on the CSF. And they didn't see a big difference in the frequency of these neurocognitive impairments.
The penetration on the CSF might not be that relevant when the drugs get into the tissue as opposed to crossing the blood-brain barrier and getting into the CSF. Obviously, we are not going to be doing biopsies of the brain in people. So any drug that suppresses viral replication probably is active within the brain tissue, even if it doesn't cross the blood-brain barrier.
But there are a lot of people, particularly neurologists, who think we should try to give medications that penetrate well in the CSF. I don't think the evidence is there yet to prove that that prevents neurocognitive impairment. And in fact, I think the evidence is the other way around: that any drug that will suppress viral replication will decrease the risk of these complications.
Myles Helfand: So if you have a patient who is on suppressive antiretroviral therapy, and maybe has been for, let's say, 15 years or so, or even longer, but is starting to develop some symptoms of early onset dementia -- maybe they are developing some memory problems, or similar CNS-related issues -- you wouldn't suggest maybe a shift to a drug that has been found through study to penetrate the blood-brain barrier a little bit better?
Pablo Tebas: With a patient like that, you start worrying about other causes of dementia -- vascular [disease], or degenerative [disorders], or Alzheimer's. You have to do a real workup for dementia before blaming it on the drugs that do not penetrate [the CSF]. So a patient that has neurocognitive impairment, in spite of successful antiretroviral therapy, I think needs a complete workup by an HIV doctor, and also by a neurologist, to try to rule out other causes of dementia that patients with HIV are not protected from. I mean, patients with HIV are aging like the general population, and they will have the problems that the general population has.
In the course of that evaluation -- which probably will include an MRI [magnetic resonance imaging], and probably a spinal tap -- I will measure the viral load in the CSF. If it's positive, and it's different from the general circulation, probably I will change the antiretroviral therapy. If the viral load is undetectable in the CSF, as it is in the serum, then I will probably think that the cause of that neurocognitive impairment doesn't have anything to do with ongoing HIV infection, and probably will not adjust the antiretroviral regimen that the patient is taking.
I think it's something that we need to worry about, and make sure that we monitor for. If it appears, then [we need to] consider more thorough evaluation of the neurocognitive function and possibly other causes that can be associated with neurocognitive impairment.
Myles Helfand: I suppose that, as with all things, there's a certain amount of perspective that this needs to be placed in. You had mentioned earlier in our talk about CNS issues that the studies that were presented here generally found that we're talking about very subtle shifts, right, in CNS function? We're not talking about anything that's necessarily something that a person would even notice in their day-to-day lives. So it's not something that we necessarily need to actively monitor, or that an HIV-infected patient, the average patient, even needs to be that concerned about, right?
Pablo Tebas: I agree with you completely. It's not that our clinics are full of patients with severe neurocognitive impairment who cannot drive to the clinic. This is not what we saw in 1990-1991, when HIV dementia was so prevalent and so disheartening because many, many people were developing it, HIV was progressing, and they were losing all of their mental capabilities.
I think, if you come to our office, or any office with HIV, patients with severe neurologic dysfunctions are rare. Occasionally, we have some. But in general patients the effect of antiretroviral treatment has been incredible, and basically AIDS-associated dementia has almost disappeared from our clinics. In some neurology clinics, I'm sure they see some of it. But as soon as we start treating HIV with potent antiretroviral therapy, and you control HIV replication, the severe neurocognitive impairment tends to improve. Then you are left with these subtle abnormalities that you just have to monitor and deal with.
Usually patients can deal with them with extra support from their surroundings. And if they have small memory losses, there are tricks to go around it. It's probably one of the reasons why GPSes [global positioning systems] for cars have become so popular.
No comments have been made.
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