HAART therapy has led to a significant reduction of general and neurological morbidity, and mortality among HIV-1 infected patients. It can also decrease HIV-1 RNA titres in plasma and CSF towards undetectable level. However, the initial hope of achieving total eradication of the virus from the body has vanished. Even in patients who do not develop viral resistance or treatment intolerance, two kinds of viral persistence have been demonstrated both in lymphoid and central nervous system. The first one is a smoldering infection that persists, despite prolonged and apparently efficient HAART, in monocytes, tissue macrophages and most probably microglia. The second one is an integration of proviral DNA in the genome of subpopulations of CD4 lymphocytes of patients receiving efficient HAART. A similar viral integration in astrocytes and less likely in resting microglia is suggested by several studies, although it has yet to be demonstrated conclusively.