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The purpose of the present review is to describe the major barriers to HIV eradication and assess the most promising cure strategies under investigation.There are significant challenges to achieve HIV eradication. These include the establishment of persistent latently infected cells, systemic chronic immune activation, and immune dysfunction. Since the announcement of the first HIV cure involving the Berlin patient, several attempts to reproduce these results have failed. Thus, it is widely accepted that long-term HIV remission would be a more feasible approach. Optimization of ART, immune-based therapies, therapeutic vaccinations, and gene editing, amongst others, are strategies aimed at controlling HIV in the absence of ART. These new strategies alone or in combination are being developed in preclinical studies and clinical trials and will provide further insight into whether long-term HIV remission is possible.The present review discusses several mechanisms that mediate the persistence of the HIV reservoir, clinical cases that provide hope in finding a functional cure of HIV, and promising interventional strategies being tested in preclinical studies and clinical trials that attempt to reduce the HIV reservoirs and/or boost the immune responses to control HIV in the absence of ART.