Today HIV infection cannot be cured due to the presence of a reservoir of latently infected cells inducing a viral rebound upon treatment interruption. Hence, the latent reservoir is considered as the major barrier for an HIV cure. So far, efforts to completely eradicate the reservoir via a shock-and-kill approach have proven difficult and unsuccessful. Therefore, more research has been done recently on an alternative block-and-lock functional cure strategy. In contrast to the shock-and-kill strategy that aims to eradicate the entire reservoir, block-and-lock aims to permanently silence all proviruses, even after treatment interruption. HIV silencing can be achieved by targeting different factors of the transcription machinery. In this review, we first describe the underlying mechanisms of HIV transcription and silencing. Next, we give an overview of the different block-and-lock strategies under investigation.
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