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