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Modeling the Effects of Vorinostat Reveals both Transient and Delayed HIV Transcriptional Activation and Minimal Killing of Latently Infected Cells


Combination antiretroviral therapy (cART) for HIV infection must be taken for life due to the existence of long lived latently infected cells. Recent efforts have focused on developing latency reversing agents to eliminate latently infected cells by activating HIV production. In this work, we assess the impact of a latency reversing agent, vorinostat, by fitting dynamic models to data from a clinical trial. Results show that vorinostat treatment induces HIV transcription transiently and that the sustained induction of HIV transcription may depend on the temporal impact of vorinostat on host gene expression. Our results also suggest that vorinostat treatment is not sufficient to induce killing of latently infected cells in a majority of HIV-infected individuals on cART.


Vyšlo v časopise: Modeling the Effects of Vorinostat Reveals both Transient and Delayed HIV Transcriptional Activation and Minimal Killing of Latently Infected Cells. PLoS Pathog 11(10): e32767. doi:10.1371/journal.ppat.1005237
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005237

Souhrn

Combination antiretroviral therapy (cART) for HIV infection must be taken for life due to the existence of long lived latently infected cells. Recent efforts have focused on developing latency reversing agents to eliminate latently infected cells by activating HIV production. In this work, we assess the impact of a latency reversing agent, vorinostat, by fitting dynamic models to data from a clinical trial. Results show that vorinostat treatment induces HIV transcription transiently and that the sustained induction of HIV transcription may depend on the temporal impact of vorinostat on host gene expression. Our results also suggest that vorinostat treatment is not sufficient to induce killing of latently infected cells in a majority of HIV-infected individuals on cART.


Zdroje

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