Nine clinical trials have analyzed whether the use of lopinavir-ritonavir (LPV/r) monotherapy could be a valid alternative to triple antiretroviral therapy. Four of these clinical trials included an analysis of risk factors for virological failure. The MONARK study evaluated monotherapy in treatment-naïve patients. The M03-613 trial evaluated monotherapy after a period of induction therapy with triple combination antiretroviral therapy. The study by Sprinz et al and the OK studies evaluated monotherapy as maintenance of virological suppression. The efficacy of monotherapy varied according to the scenario. In the scenario of induction-maintenance, the factors related to virological failure were suboptimal adherence and low baseline CD4 counts. In the scenario of maintenance, the factors related to virological failure were suboptimal adherence, nadir CD4 count and low hemoglobin. In treatment-naive patients, the risk of virological failure increased in patients who did not achieve a viral load of less than 400 copies/ml 4 weeks after initiating treatment and in those infected with non-B subtypes (a factor that was probably also related to suboptimal adherence).