Low-level HIV-1 replication and the dynamics of the resting CD4+ T cell reservoir for HIV-1 in the setting of HAART

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Sedaghat, Ahmad R.
Siliciano, Robert F.
Wilke Claus O.

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BMC Infectious Diseases


Background: In the setting of highly active antiretroviral therapy (HAART), plasma levels of human immunodeficiency type-1 (HIV-1) rapidly decay to below the limit of detection of standard clinical assays. However, reactivation of remaining latently infected memory CD4+ T cells is a source of continued virus production, forcing patients to remain on HAART despite clinically undetectable viral loads. Unfortunately, the latent reservoir decays slowly, with a half-life of up to 44 months, making it the major known obstacle to the eradication of HIV-1 infection. However, the mechanism underlying the long half-life of the latent reservoir is unknown. The most likely potential mechanisms are low-level viral replication and the intrinsic stability of latently infected cells. -- Methods: Here we use a mathematical model of T cell dynamics in the setting of HIV-1 infection to probe the decay characteristics of the latent reservoir upon initiation of HAART. We compare the behavior of this model to patient derived data in order to gain insight into the role of low-level viral replication in the setting of HAART. -- Results: By comparing the behavior of our model to patient derived data, we find that the viral dynamics observed in patients on HAART could be consistent with low-level viral replication but that this replication would not significantly affect the decay rate of the latent reservoir. Rather than low-level replication, the intrinsic stability of latently infected cells and the rate at which they are reactivated primarily determine the observed reservoir decay rate according to the predictions of our model. -- Conclusion: The intrinsic stability of the latent reservoir has important implications for efforts to eradicate HIV-1 infection and suggests that intensified HAART would not accelerate the decay of the latent reservoir.


Ahmad R. Sedaghat and Robert F. Siliciano are with the Department of Medicine, Johns Hopkins University School of Medicine, Baltimore Maryland 21205, USA -- Robert F. Siliciano is with the Howard Hughes Medical Institute, Baltimore Maryland 21205, USA -- Claus O. Wilke is with the Section of Integrative Biology, Center for Computational Biology and Bioinformatics, and Institute for Cell and Molecular Biology, University of Texas at Austin, Austin, TX 78713, USA

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Sedaghat, Ahmad R., Robert F. Siliciano, and Claus O. Wilke. “Low-Level HIV-1 Replication and the Dynamics of the Resting CD4+ T Cell Reservoir for HIV-1 in the Setting of HAART.” BMC Infectious Diseases 8, no. 1 (January 2, 2008): 2. doi:10.1186/1471-2334-8-2.