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CNS penetration - Sustiva vs Viramune

Apr 15, 2007

Can you tell me if these achieve similar levels of CNS penetration? (I want to keep HIV-related dementia risk low.) I'm thinking of switching to Viramune because after 3 months, I still feel sleepy during the day - even if I get 7 - 8 hours of sleep. I drink at least 10 cups of tea and have doubled my ritalin dose from 10mg to 20mg every three hours (I still barely feel the ritalin, even at this dosage!), just to get through the day (I have ADD). My VL is now undetectable and my CD4s have stablized at 250. I'm tired of the sleepy / hung over feeling. It has improved lately, but I don't feel all the way back to my pre-meds mental clarity. I have a really intellectually challanging job and this issue is hard to cope with as I feel dumbed down.

Response from Dr. Wohl

This is a good question that raises a couple of important issues. The first is the relative penetration of various HIV meds into the central nervous system (CNS) and the second is whether the level of drug in the CNS matters when it comes to preventing or treating HIV dementia.

As far as the first issue, Sustiva clearly does get into the CNS - as evidenced by the side effects this agent can produce (dizziness, vivid dreams, etc). But, surprisingly, the levels of Sustiva in the CNS are not all that high relative to other HIV meds. As Dr. David Simpson, a neurologist who specializes in HIV has written on this site, "Agents shown to have the best cerebral spinal fluid (CSF) penetration include AZT, D4T, abacavir, nevirapine (Viramune), and indinavir." (

But, Dr. Simpson points out that drug penetration is not everything. "In addition to the absolute drug concentration in the CSF, one must consider how effectively the drug inhibits viral replication. Thus, some agents such as efavirenz (Sustiva), with only little CSF penetration, are likely to reach CSF levels that exceed IC95." That is, the level of the drug found in the CSF is high enough to inhibit the replication of HIV by 95%.

The second issue is whether more drug in the CSF equals better prevention and treatment of HIV-related CNS problems. Here the data are a bit mixed and while it makes sense that HIV meds that are able to get into the CSF will work the best to treat and prevent HIV dementia some studies support this but others do not. If you actually had dementia, I would hedge my bets and attempt to use of drugs with excellent activity in the CNS. Given current understanding, however, I would generally not include protection against dementia as a factor to consider when chosing HIV meds.

In your specific case, Viramune does get into the CNS well so this should allay some of your concern. If you want/need to switch, I think you can safely do so.


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