Abacavir/lamivudine (ABC/3TC) and tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) are widely used as first-line antiretroviral therapies. However, there are limited data comparing the safety of these therapies with long-term use. The objective of this study was to assess the long-term safety of these commonly used first-line nucleoside/nucleotide combinations each administered with efavirenz (EFV).