We report in this study that minimum productive HIV infection in astrocytes (a predominant cell type in brain and persists for the entire life) occurs through endocytosis. The lysosomotropic agent chloroquine enhanced permissiveness of astrocytes to HIV infection possibly by circumventing degradation of endosome-entrapped viral particles. In particular, chloroquine may promote establishment of a stable long term viral reservoir in astrocytes and may eventually facilitate early onset of neurological complications.