The Depsipeptide Romidepsin Reverses HIV-1 Latency

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One proposed way of curing HIV is to activate virus transcription and kill latently infected cells while the presence of antiretroviral therapy prevents spreading the infection. Induction of global T cell activation by mitogenic or other potent activators effectively reverses HIV-1 from latency ex vivo, but such compounds are generally too toxic for clinical use. Therefore, investigating the capacity of small molecule latency reversing agents to induce production of virus without causing global T cell activation has been a top research priority for scientists in recent years. In the present clinical trial, we demonstrate that significant viral reactivation can be safely induced using the depsipeptide romidepsin (HDAC inhibitor) in long-term suppressed HIV-1 individuals on antiretroviral therapy. Following each romidepsin infusion, we observed clear increases in lymphocyte H3 acetylation, HIV-1 transcription, and plasma HIV-1 RNA. Importantly, this reversal of HIV-1 latency could be measured using standard clinical assays for detection of plasma HIV-1 RNA. Furthermore, romidepsin did not alter the proportion of HIV-specific T cells or inhibit T cell cytokine production which is critically important for future trials combining HDAC inhibitors with interventions (e.g. therapeutic HIV-1 vaccination) designed to enhance killing of latently infected cells.

Vyšlo v časopise: The Depsipeptide Romidepsin Reverses HIV-1 Latency. PLoS Pathog 11(9): e32767. doi:10.1371/journal.ppat.1005142
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005142

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