At least nine different genetic HIV-1 subtypes and several circulating recombinant forms exist, which in addition to HIV-1 subgroups and HIV-2 account for the global AIDS pandemic. Even though HIV-1 subtype C and A predominate globally, antiretroviral drugs have been designed based on sequences of clade B reverse transcriptase (RT) and protease enzymes due to the domination of HIV-1 subtype B in highly industrialized countries. Since there is no clarity about possible effects of the genetic diversity of HIV-1 on therapy outcome and drug resistance, multiple studies have been performed with divergent results. Up to now this question remains to be answered.