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Relationship between Preexisting Latent Viral Reservoirs and the Reemergence of Plasma Viremia after Discontinuation of Highly Active Antiretroviral Therapy T. W. CHUN*1, R. DAVEY1, M. OSTROWSKI1, D. ENGEL1, J. MULLINS2, C. LANE1, and A. FAUCI1. 1NIAID, NIH, Bethesda, MD; and 2Univ. of Washington, Seattle The persistence of a pool of latently infected, resting CD4+ T cells carrying replication-competent HIV has been well documented in HIV-infected individuals who are receiving highly active antiretroviral therapy (HAART) and in whom successful suppression of plasma viremia has been achieved. Although this latent viral reservoir is considered to be a major impediment to complete eradication of HIV in infected individuals receiving HAART, the pathologic significance of this viral reservoir as well as its role in the rebound of plasma viremia after discontinuation of HAART is largely unknown. Using quantitative coculture and heteroduplex tracking assays, we demonstrate that the pool of latently infected, resting CD4+ T cells does not account entirely for the early rebounding plasma HIV in infected individuals in whom HAART has been discontinued, even after prolonged periods of successful suppression of plasma viremia. There was no correlation between the kinetics of viral rebound in plasma upon cessation of HAART and the size of the pool of the latent HIV reservoir prior to discontinuation of therapy. In addition, HIV env of the rebounding plasma virus was genetically distinct from either cell-associated HIV RNA or replication-competent virus within the pool of latently infected, resting CD4+ T cells in the majority of patients examined. These results underscore the possibility of existence of other persistent HIV reservoirs that could prompt rapid emergence of plasma viremia following cessation of HAART and the necessity to develop therapies directed toward such populations of infected cells. Key Words: HAART, latency, viral reservoirs |
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© 7th
Conference on Retroviruses and Opportunistic Infections, |