F-106 Clonally-amplified proviruses as reservoirs of HIV

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Abstract

In 2014, clonal expansion of HIV-infected cells was first described as a mechanism of HIV-1 persistence on antiretroviral therapy (Maldarelli et al and Wagner et al. Science). It was initially not known whether clonally-amplified proviruses were intact, ie., capable of producing infectious virus. Subsequently, one case of a clonally-amplified provirus that produced infectious viremia was reported in an individual with metastatic squamous cell carcinoma (Simonetti et al. PNAS 2016). We have since performed a series of studies in individuals started on ART at various stages of HIV infection to identify other clonally-amplified proviruses, including defective and intact ones, and to characterize their integration sites, dynamics of outgrowth, transcriptional activity at the single cell level, virus production, and cell origin. Findings from these studies will be presented and their implications for HIV cure strategies will be discussed.

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