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Likelihood of developing dementia
Jan 2, 2004

Hello,

I have had HIV since late 1982 and discovered it (along with an AIDS dx) in 1995.

Currently, I have 190 T-cells (highest ever) and undetectable viral load.

I am on my 3rd drug combination, which includes Kaletra, ddi, and 3TC. I also take Septra (I had PCP), acyclovir, and a number of other medications for pain (sciatica) and depression.

My question is: I am pretty sure none of the anti-HIV drugs I've been taking (the ones listed above) for the past 2+ years cross the blood-brain barrier. I have heard that the rate of AIDS-related dementia is about 10% now, with the new drugs. But I assume that means if one takes drugs (such as AZT) that pass the blood-brain barrier.

So, in short, can you tell me if I am at strong risk of developing dementia with this drug regimen?

Thank you!

Colleen

Response from Dr. Horwath

The risk factors for the development of HIV-associated dementia (HAD)are not fully understood. We know that a viral load of >30,000 copies/ml is associated with an 8.5 times higher risk of developing HAD, when compared to having a high viral load <3,000 copies/ml. We also know that a CD4 count <200 is associated with a 3.5 times higher risk of dementia, when compared to a CD4 count of >500.

You are correct in observing that some HAART drugs penetrate the blood-brain barrier better than others. Lamivudine (3TC), stavudine (d4T), and zidovudine (AZT) are known to have excellent penetration of the blood-brain barrier.

Only AZT at high doses (2 grams/day) has been shown to improve signs and symptoms of dementia in a double blind, placebo controlled clinical trial. Such doses are no longer used because they are not well tolerated (and not necessary when AZT is used as part of a HAART regimen).

HAART has decreased the incidence of new cases of dementia, but has not prevented dementia altogether. It is thought that the benefits of HAART in relation to dementia are mediated by decreasing the viral load. However, comparative longitudinal studies testing the merits of different regimens in terms of their effects on dementia or dementia prevention have not been done. The advantages of drugs that penetrate the blood-brain barrier are largely theoretical at this point, in the absence of careful follow-up studies.

Other drugs that are known to have adequate penetration of the blood-brain barrier are indinavir and nevirapine, but studies of their relative merits in treating or preventing demntia have not been done.



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