The strategy of induction-maintenance therapy with lopinavir-ritonavir (LPV7r) consists of initiating antiretroviral therapy in a treatment-naïve patient with two nucleosides plus LPV/r. When the patient has achieved an undetectable HIV RNA viral load of < 50 copies/mL for a specified time period, the nucleosides are withdrawn and the patient continues to receive antiretroviral therapy with LPV/r monotherapy. The induction-maintenance strategy with LPV/r has been analyzed in the M03-613 clinical trial. In this trial, antiretroviral-naïve patients were randomized to receive zidovudine/lamivudine plus LPV/r (n = 104) or efavirenz (n = 51). In patients randomized to receive LPV/r who achieved an HIV RNA viral load of < 50 copies/mL for 3 consecutive months, nucleoside therapy was suspended. In an intention-to-treat analysis (missing equals failure), 60% of the patients randomized to receive LPV/r and 63% of those randomized to receive efavirenz maintained an HIV RNA viral load of < 50 copies/mL at 96 weeks of follow-up (p = 0.73; 95% confidence interval for the difference -19% to 13%). Moreover, this study showed that patients randomized to LPV/r experienced less lipoatrophy than those randomized to efavirenz. The M03-613 trial suggests that the induction-maintenance strategy with LPV/r is safe in most patients. However, rates of virological efficacy are lower than those achieved with the simplification strategy. Moreover, this trial demonstrates that LPV/r monotherapy may have major benefits in peripheral fat preservation.