Although　oral　combination　antiretroviral　therapy　effectively　clears　plasma　HIV,　patients　on　oral　drugs　exhibit　much　lower　drug　concentrations　in　lymph　nodes　than　blood.　This　drug　insufficiency　is　linked　to　residual　HIV　in　cells　of　lymph　nodes.　While　nanoformulations　improve　drug　solubility,　safety　and　delivery,　most　HIV　nanoformulations　are　intended　to　extend　plasma　levels.　A　stable　nanodrug　combination　that　transports,　delivers　and　accumulates　in　lymph　nodes　is　needed　to　clear　HIV　in　lymphoid　tissues.　This　review　discusses　limitations　of　current　oral　combination　antiretroviral　therapy　and　advances　in　anti-HIV　nanoformulations.　A　＇systems　approach＇　has　been　proposed　to　overcome　these　limitations.　This　concept　has　been　used　to　develop　nanoformulations　for　overcoming　drug　insufficiency,　extending　cell　and　tissue　exposure　and　clearing　virus　for　treating　HIV/AIDS.