OBJECTIVES: Current antiretroviral (ARV) therapy has transformed HIV from an acute to a chronic disease. Consequently, there are more patients living with HIV and the cost burden to societies that provide lifetime healthcare, such as Colombia, is increasing.  The value assessment of ARV regimens, therefore, requires a lifetime horizon to accommodate implications of failure, resistance, switching and survival.  The objective was to perform a cost-effectiveness analysis of two first-line protease inhibitor-based regimens for HIV-infected, ARV-naïve patients in Colombia: LPV/r versus DRV+RTV. METHODS: A previously published discrete event simulation model of first-line LPV/r and DRV+RTV was adapted to comprehensively represent HIV management in Colombia.  The impact of initial treatment on CD4 cell count, viral load, adherence, virologic suppression/failure/rebound, acquired resistance, and ensuing treatment changes were based on ARTEMIS trial data and the clinical literature.  Up to 3 regimen changes were permitted over the model’s lifetime horizon.  Cardiovascular risk was based on the Framingham risk score.  Clinical measures included AIDS related and non-AIDS related events, AEs, time on sequential therapies, and cardiovascular events.  Outcomes included lifetime costs and quality adjusted life years (QALYs), discounted at 3% per annum.  Perspective was the Colombian national healthcare system.  Costs for ARVs and medical management were referenced to Colombia pesos (COP). RESULTS: Initiating LPV/r over DRV+RTV saved COP7,845,894 per patient over a lifetime with similar life expectancy (+0.02 years; -0.03 QALYs).  Similar rates of death, AIDS events, cancer, and lipoatrophy/lipodystrophy were predicted for both groups.  Lifetime cost of cardiovascular events were COP70,020 per patient less in the LPV/r arm.  LPV/r was cost saving at 5 years (COP11,311,677) and was cost-effective across multiple sensitivity analyses. CONCLUSIONS: Initiating HIV infected, ARV-naïve patients on a LPV/r-based regimen compared to a DRV+RTV-based regimen is cost saving and provides similar life expectancy.  Sensitivity analyses provided confidence around these point estimates.