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Lasting off-drug antiretroviral activity by deferiprone in isolate-infected, long-term replenished primary cell cultures.

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posted on 2016-05-18, 08:40 authored by Deepti Saxena, Michael Spino, Fernando Tricta, John Connelly, Bernadette M. Cracchiolo, Axel-Rainer Hanauske, Darlene D’Alliessi Gandolfi, Michael B. Mathews, Jonathan Karn, Bart Holland, Myung Hee Park, Tsafi Pe’ery, Paul E. Palumbo, Hartmut M. Hanauske-Abel

Long-term replenished primary cell cultures were infected with isolate #990,010 on Day 0 as described [43] and replenished as indicated by arrowheads; on each occasion, half of the culture was replaced. After one week to establish infection ex vivo (period 1), cultures were treated with 200 μM deferiprone for one month (period 2), then the drug was withdrawn (asterisk) and the cultures were assayed for viral copy number during three post-treatment months to monitor for re-emerging productive infection (period 3). Each p24 value is expressed relative to the respective p24 control on the day of each measurement. Due to the continuous replenishment with freshly isolated uninfected primary cells, the viability was consistently above 95% as assessed by computerized trypan blue exclusion. The detection limits of the HIV-1 RNA assays are indicated. p24 assays: Open circle, HIV-exposed untreated cultures; closed circles, HIV-exposed cultures, treated with deferiprone. HIV-1 RNA assays: Open squares, HIV-exposed untreated cultures; closed triangles, HIV-exposed cultures during deferiprone treatment; open triangles, HIV-exposed cultures after withdrawal of deferiprone; blue, control parameters.

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