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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. 1) Remission of acute infection in macaques induced by ART (AZT, ddI, indinavir).

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Reservoirs and Mechanism of Disease Progression

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  1. Reservoirs and Mechanism of Disease Progression

  2. Reservoirs • Latently infected T-cells • Residual viral replication • Anatomical sanctuaries

  3. Acute HIV Infection

  4. 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 Hocqueloux L, et al. AIDS. 2010 Jun 19;24(10):1598-601. 3) Reduction of the viral reservoir in humans treated with mega ART (tenofovir emtricitabine/efavirenz/raltegravir/ maraviroc) at acute infection Ananworanich J, et al. CROI. 2011. 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 Benlhassan-Chahour, K. et al. 2003. J. Virol. 77(23):12479-12493

  5. Absolute CD4 counts, and their slopes, identify the viral reservoir Chomont et al.,Nat Med 2009 Lewis et al.,AIDS 2011

  6. Reservoirs Latently infected T-cells Residual viral replication Anatomical sanctuaries

  7. Main latent virus reservoirs: central memory (TCM) and transitional memory (TTM) CD4+ T-cells

  8. Auranofin: an “anti-memory” drug Lewis et al., AIDS 2011

  9. 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

  10. Reservoirs Latently infected T-cells Residual viral replication Anatomical sanctuaries Immune activation

  11. Lafeuillade et al., HIV Clin Trials 2009

  12. Immune activation identifies the HIV-1 reservoir Savarino et al., Lancet Infect Dis 2003 Chomont et al., Nat Med 2009 HCQ: hydroxychloroquine Piconi et al., Blood 2011

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