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H.A.N.D and brain penetration of anti-virals.
Jun 7, 2014

Dear Dr Young,

The last few months I have noticed a worrying trend as regards mood swings, anxiety and depressive like symptoms, including angry episodes. Cognitively, I haven't noticed any significamt difference, although I am concerned about HAND - HIV associated neurocognitive disorder, and it's possible manifestation in my case.

I have been undetectable on my current regimin of boosted Darunavir and Maraviroc for four years now and previously a year suppressed on Atazanavir, tenofovir, combivir. Despite being put on meds within a few months of infection, my CD4 has stubbornly remained around 250. I have the transmitted mutation T215S which knocks out AZT in combivir?, and unknown tropism, after three failures to amplify a sample from undetectable. My adherence is around 99.9%. So, my question, based on these observations and background is could it be possible that depite viral control in the blood, there is inadequate penetration in the brain? If I am mixed tropic, would this effectively equate to just activity of Darunavir in the brain, allowing ongoing replication and these symptoms I've recently experienced? Does excellent adherence reduce the liklihood of CNS viral escape as well as in the blood?

Finally, could ongoing CNS replication of HIV activate the JC virus and lead to the devasting complication of PML in the context of my lowish CD4 count?

Thanks, Mark.

Response from Dr. Young

Hello Mark and thanks for posting your interesting question.

At first glance, it seems like your symptoms are more mood related than cognitive. That said, cognitive problems are disturbingly common and sometimes asymptomatic. We use (as is recommended by the NY State AIDS Institute and European AIDS Clinical Society/EACS) the International HIV Dementia Scale as a tool to screen if one has cognitive problems. The test is used to determine if there's reason to do more detailed neurocognitive testing. IHDS is a simple test and easy to implement.

If your testing is indeed positive, then there's a lot of debate about what to do next. The EACS Guidelines offer some pragmatic things to do. Aside from cognitive testing, considering a spinal tap and viral load test on the spinal fluid will help determine if there is any replicating virus around your brain. If detected, resistance testing is recommended. Absent that, while it seems reasonable (as you suggest) that you should take medications that effectively penentrate the brain, a recent published study disappointingly found no benefit in this strategy. For what it's worth, both darunavir and maraviroc are thought to have very good penetration into the spinal fluid.

Interesting, several recently published reports suggest benefit in an active lifestyle or physical exercise.

Lastly, I'd doubt the JC virus would explain your symptoms, and PML is generally only found in people whose CD4s are less than 100.

For more information about neurocognitive illness and HIV, check out our pages on myHIVclinic.org.

Hope that's helpful, BY



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