We have seen four decades of human struggle to cure or eradicate HIV infection since the first clinical detection of HIV infection. Various developed drugs such as nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors, integrase inhibitors, microbicides, and others have known restrictions, such as side effects and resistance development when used alone, and hidden reservoir of the virus, which have opened the gates for the involvement of nanomedicine associated systems, particularly for latent sites of HIV infection. The nanotechnological vehicles, such as liposomes, dendrimers, metal nanoparticles, polymeric nanocapsules/particles, surfactants, and targeted vehicles have become part of extensive studies for application in real settings for the delivery of NRTIs, NNRTIs, microbicides, and siRNA. The positional standing of research in quest of potential therapeutics for combating HIV infection in reference for four decades with this virus need a rational evaluation of nanotechnology to achieve a practical solution to save the lives
