Reservoirs and Mechanism of Disease Progression
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Transcript of Reservoirs and Mechanism of Disease Progression
Reservoirs and Mechanism of Disease Progression
Reservoirs
• Latently infected T-cells
• Residual viral replication
• Anatomical sanctuaries
Acute HIV Infection
Benlhassan-Chahour, K. et al. 2003. J. Virol. 77(23):12479-12493
FIG. Effect of HAART on plasma viral load (top panels) and on proliferation of NK cells and CD4+ and CD8+ T lymphocytes (middle and bottom panels) in macaques treated with HAART after SIV exposure
Hocqueloux L, et al. AIDS. 2010 Jun 19;24(10):1598-601.
Ananworanich J, et al. CROI. 2011.
1) Remission of acute infection in macaques induced by ART (AZT, ddI, indinavir)
2) Remission in humans treated with ART (optimized background therapy) at acute infection
3) Reduction of the viral reservoir in humans treated with mega ART (tenofovir emtricitabine/efavirenz/raltegravir/maraviroc) at acute infection
Absolute CD4 counts, and their slopes, identify the viral reservoir
Chomont et al., Nat Med 2009 Lewis et al., AIDS 2011
Reservoirs
• Latently infected T-cells
• Residual viral replication
• Anatomical sanctuaries
Main latent virus reservoirs: central memory (TCM) and transitional memory (TTM) CD4+ T-cells
Lewis et al., AIDS 2011
Auranofin: an “anti-memory” drug
Effect of an in-vivo treatment consisting of intensified ART (iART) plus the anti-reservoir drug auranofin on
viral DNA in PBMCs of SIV+ macaques
Lewis et al., AIDS 2011
Reservoirs
• Latently infected T-cells
• Residual viral replication
• Anatomical sanctuariesImmune activation
Lafeuillade et al., HIV Clin Trials 2009
Immune activation identifies the HIV-1 reservoir
HCQ: hydroxychloroquine
Chomont et al., Nat Med 2009
Piconi et al., Blood 2011
Savarino et al., Lancet Infect Dis 2003