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Rapamycin tones down the toxicity of HIV-1 reactivation strategies

JCI Journals

Although patients infected with HIV-1 can successfully manage the disease by taking antiretroviral therapies, these therapies cannot completely eradicate the virus because HIV-1 can persist in a latent reservoir of T cells without replicating. More complete eradication of HIV-1 infection could be achieved using therapies that reactivate the virus in the latent reservoir, but the existing strategies are considered too toxic to use as treatments in HIV-1 patients. This week in the JCI, work performed in Robert Siliciano's lab at Johns Hopkins University School of Medicine evaluated whether a strategy combining T cell activation with the immunosuppressive drug rapamycin could reactivate latent HIV-1 reservoirs without causing toxic side effects. Rapamycin treatment reduced proinflammatory cytokine release and other signs of toxicity without decreasing HIV-1 reactivation in T cells from HIV-1-infected individuals. Importantly, the rapamycin treatment did not impair the ability of the immune system to recognize infected T cells. These findings indicate that rapamycin could be used to reduce the toxicity of strategies targeting the HIV-1 latent reservoir.


TITLE: Rapamycin-mediated mTOR inhibition uncouples HIV-1 latency reversal from cytokine-associated toxicity


Robert F. Siliciano
Johns Hopkins University School Of Medicine

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