Simplified antiretroviral regimens have been developed with the aim of improving treatment adherence and quality of life of HIV-infected patients. The single-class triple-nucleoside reverse transcriptase inhibitor combination has contributed to the improvement of the management of HIV infection, especially in patients with adherence problems and special groups of the patient population. Such a regimen remains an alternative option because of lower virological efficacy compared with the preferred multiclass antiretroviral regimens. However, recently, a nucleoside reverse transcriptase inhibitor abacavir/lamivudine/zidovudine plus tenofovir has been investigated in both antiretroviral-naive patients and in heavily pre-treated patients, as well in the setting of simplification/switching strategies. This experimental combination could be a safe and attractive option that offers the advantages of limited toxicity, few drug interactions and the use of future treatment options with new drugs, especially for patients in later stages of infection.