Low-Level HIV-I Replication and the Dynamics of the Resting CD4(+) T Cell Reservoir for HIV-I in the Setting of HAART

dc.contributor.utaustinauthorWilke, Claus O.en_US
dc.creatorSedaghat, Ahmad R.en_US
dc.creatorSiliciano, Robert F.en_US
dc.creatorWilke, Claus O.en_US
dc.date.accessioned2016-10-28T19:49:21Z
dc.date.available2016-10-28T19:49:21Z
dc.date.issued2008-01en_US
dc.description.abstractIn the setting of highly active antiretroviral therapy (HAART), plasma levels of human immunodeficiency type-I (HIV-I) 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-I 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-I 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-I infection and suggests that intensified HAART would not accelerate the decay of the latent reservoir.en_US
dc.description.departmentIntegrative Biologyen_US
dc.description.sponsorshipNIH AI 065960, AI 143222, AI 51178en_US
dc.description.sponsorshipDoris Duke Charitable Foundationen_US
dc.description.sponsorshipThe Howard Hughes Medical Instituteen_US
dc.identifierdoi:10.15781/T28W38506
dc.identifier.citationSedaghat, 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, Vol. 8, No. 1 (Jan., 2008): 2.en_US
dc.identifier.doi10.1186/1471-2334-8-2en_US
dc.identifier.issn1471-2334en_US
dc.identifier.urihttp://hdl.handle.net/2152/43143
dc.language.isoEnglishen_US
dc.relation.ispartofen_US
dc.relation.ispartofserialBMC Infectious Diseasesen_US
dc.rightsAdministrative deposit of works to Texas ScholarWorks: This works author(s) is or was a University faculty member, student or staff member; this article is already available through open access or the publisher allows a PDF version of the article to be freely posted online. The library makes the deposit as a matter of fair use (for scholarly, educational, and research purposes), and to preserve the work and further secure public access to the works of the University.en_US
dc.rights.restrictionOpenen_US
dc.subjecthuman-immunodeficiency-virusen_US
dc.subjectactive antiretroviral therapyen_US
dc.subjectlatenten_US
dc.subjectreservoiren_US
dc.subjectcombination therapyen_US
dc.subjectdrug-resistanceen_US
dc.subjectinfected individualsen_US
dc.subjectlifelong persistenceen_US
dc.subjectviral persistenceen_US
dc.subjecttype-1 infectionen_US
dc.subjectrapiden_US
dc.subjectturnoveren_US
dc.subjectinfectious diseasesen_US
dc.titleLow-Level HIV-I Replication and the Dynamics of the Resting CD4(+) T Cell Reservoir for HIV-I in the Setting of HAARTen_US
dc.typeArticleen_US

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