Genetically distinct HIV-1 variants in cerebrospinal fluid and plasma during ART

[oksikoko]

Do any of you have thoughts on this? From the Journal of Infectious Diseases:

“We sequenced HIV-1 in 70 CSF and 29 plasma samples and the corresponding pre-therapy samples from 17 subjects on suppressive therapy. More of the CSF sequences were hypermutants than plasma sequences. We generated on-therapy sequences from both CSF and plasma from two subjects; in one we found genetically distinct sequences in CSF and plasma indicating that they came from two different compartments, one potentially the CNS, during suppressive therapy. In addition, there was little evidence of viral evolution in the CSF during therapy, suggesting that continuous virus replication is not the major cause of viral persistence in the CNS.”

http://jid.oxfordjournals.org/content/early/2013/12/12/infdis.jit805.abstract

So:
1) More of the CSF sequences were hypermutants. What do they mean by hypermutants? Quickly mutating strains? Strains that mutate a lot? Strains with ADHD?

2) They found genetically distinct sequences in the blood plasma and CSF. They also found evidence suggesting that viral replication is not the major cause of viral persistence in the CNS. So, are they suggesting that both of these locations (blood and CSF) are being 'seeded' by different reservoirs (therefore different sequences) and that viral replication isn't happening in the blood or the CSF due to ART? Or that due to ART they're now closed systems and only have whatever strains were there at the onset of ART since therapy is holding further mutations at bay?

3) Is it normal with viruses and pathogens in general for there to be different “strains” (I assume this is what's meant by different genetic sequences) predominating in different body systems? I suppose with any long-lived infection, different strains would mutate and find niches in our bodies.

4) Does this mean, in theory, they should be trying to target the CNS with different medications than the ones we use to bring plasma viral loads down?

I don't need the answers to any of these for any reason. Just curious if anyone had thoughts.

Lee

Thanks,
Lee

[Tadeys]

Strains with ADHD?.....