Attacking Persistent HIV Infection: Moving Towards Eradication of HIV Infection

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Attacking Persistent HIV InfectionMoving
TowardsEradication of HIV Infection

• David M. Margolis, MD

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More than two decades ofpandemic HIV three
tools needed in the coming decades

• Prevent infection
• Prevent disease in the infected
• Eradicate infection

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Latent pool of infected resting CD4 cells
reduced by HAART during acute/early HIV infection
Imputed Size of Latent pool
Expected frequency of resting CD4 infection after
early ART Blankson et al. JID 2000
10.0
x
1.0
Infected Resting CD4 Cells per Million (log
scale)
0.1
0.01
x
EIA WB indet.(est. ART 6 mo. Post-AHI)
x
EIA - NAAT (est. ART 3 months post-AHI)
0.001
EIA - NAAT (est. ART 1 month post-AHI)
1
3
6
12
24
Months after est. date of HIV infection
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Binding, Fusion Uptake
Virion Release Maturation
Many therapies for replicating HIV None for
persistent HIV genomes
Virion Assembly
Reverse Transcription Nuclear Import
Viral Protein Production
Transcription, Splicing RNA Export
Integration
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• LSF and YY1 recruit HDAC-1 and repress the HIV-1
  LTR
• Histone deacetylase is a direct target of
  valproic acid, a potent anticonvulsant

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Depletion of latent HIV infection with Valproate
and intensive HAART
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..clearance? ..remission?