Several strategies are currently investigated to reduce the pool of all HIV-1 reservoirs in infected patients in order to achieve functional cure. The most prominent HIV-1 cell reservoirs in the brain are microglial cells. Virus infection maybe lifelong. Infected microglial cells are believed to be the source of peripheral tissues reseeding and responsible for the emergence of drug resistance. Clearing infected cells from the brain is therefore crucial. However, many characteristics of microglial cells and the central nervous system prevent the eradication of brain reservoirs. Current trials, such as “shock and kill”, the “deep and lock” and the gene editing strategies do not respond to these difficulties. Therefore, new strategies have to be designed when considering brain reservoirs such as microglial cells. We set up an original gene suicide strategy using a latently infected microglial model. In this paper we provide proof of concept of this strategy. Our results demonstrate that this strategy enables the eradication of latently-infected microglial cells.