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Very Early Viral Infection of the Central Nervous
System without Evidence of Compartmentalization During Acute HIV-1
Infection
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Reported by Jules Levin
CROI 2013
"Our results suggest that during this very early acute period there is essentially free traffic of virus from the plasma into the CSF"
Serena Spudich from Yale presented this oral presentation
"10 subjects had very consistent results, HIV in CSF and plasma was highly similar in 10 'very acute'
HIV subjects with high levels of HIV RNA."
"Not only are the sequences similar but they also have similar time to most recent ancestor characteristics and levels of within compartment diversity, one exception was 1 patient who seemed to have 2 viruses in the CSF but only 1 virus in the plasma"
"Our results suggest that during this very early acute period there is essentially free traffic of virus from the plasma into the CSF, there is not a selection pressure or some sort of genetic bottleneck that determines which virus enters the CSF preferentially and it also tells us that if we see unique quasispecies during early stages of infection that possibly this emerged as some sort of evolution after the period of acute infection"
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"for one thing CNS infection/inflammation is initiated early. Another concerning thing is that early entry of HIV into the CSF may facilitate very early establishment of CNS reservoir. This is what we are trying to assess with very early sequencing, assessing the timing of emergence of 'compartmentalization' which would suggest that HIV is produced within the nervous system. We've seen this in another cohort by about 6 months after infection-- some subjects have 'compartmentalized' CNS HIV suggesting a local reservoir."
"and this could major impact in trying to find a functional or cure right?"
"we have good evidence that HIV remains in the brain during ART, and likely continues to have an effect, but it is not yet clear to what extent it 'evolves' in the setting of treatment, except for some of the very rare cases of symptomatic CNS 'escape' (described in papers such as Canestri A CID2010, Peluso MJ AIDS 2012, etc.). We had a poster at this year's CROI (first author Dahl, with Sarah Palmer's group) trying to look at 'evolution' of HIV from the CSF of people on treatment, and basically there was too little virus there to really assess 'evolution.' "
"So other than the impact on cure or eradication what other implications does this have? over time despite successful ART HIV in the brain/CNS remains, does it evolve & what are the long-term affects in HIV+ over 55 or 60, we have really to characterize this!"
link to webcast
http://webcasts.retroconference.org/console/player/19408?mediaType=podiumVideo
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