The infection by Human immunodeficiency virus (HIV) has high incidence with 2,7 millions cases reported in 2010. Sensitive distal peripheral neuropathy (SDPN) is the most common nervous system disease caused by HIV infection. This entity characteristically painful could be associated directly to infection: polyneuropathy distal symmetric (PDS) or secondary for antiretroviral agents neurotoxicity: neuropathy toxic antiretroviral (NTA). In order to explain its physiopathology many hypothesis are proposed; the most recent hypothesis accepted suggest a synergy level between NTA and DSP, with mechanisms inflammatory in common. Other mechanisms proposed are mitochondrial dysfunction mediated by mitochondrial polymerase gamma depletion, creatine deficit and direct viral protein toxicity, especially by glycoprotein 120. Future investigations are required for developing new therapeutics targets to manage and treat NSDP.