OBJECTIVES: To determine whether, from the Swedish healthcare payer perspective etravirine is cost-effective when added to a standard highly active antiretroviral treatment (HAART) in multi-drug resistant HIV-1 infected adults. METHODS: Etravirine added to a standard regimen including darunavir/r, an optimized background regimen (OBR) of nucleoside reverse transcriptase inhibitors (NRTIs) and optionally enfuvirtide was compared to the same standard regimen alone. The target population consisted of HIV-1-infected pretreated patients with resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI) and ≥ 3 protease inhibitor (PI) mutations. Cost-effectiveness, expressed as cost per quality-adjusted life year (QALY) gained, was calculated using a lifetime Markov model. The model predicted patient flow through six health states representing CD4+ T-cell count ranges (>500, 351-500, 201-350, 101-200, 51-100 and 0-50 cells/mm3), and one absorbing ‘death’ state. After treatment failure, a switch to a raltegravir regimen was assumed. Transition probabilities describing patient flow through the model were obtained from immunologic response rates per virologic response category observed in the DUET trials for etravirine and placebo and reported in phase III trials for raltegravir. All-cause mortality was obtained from Swedish statistics. HIV-related mortality, utilities and non-ARV costs associated with each CD4+ T-cell count range were obtained from literature. Antiretroviral (ARV) drug use reflected that observed in the clinical trials. Outcomes and costs expressed in 2008 Swedish Kronor (SEK) were discounted at 3%. The impact of parameter uncertainty was explored in one-way as well as probabilistic sensitivity analysis. Variability analyses explored different model assumptions. RESULTS: The analysis predicted a gain in discounted QALYs of 0.461 and an incremental cost per QALY of SEK362,583, ranging from 240,074SEK/QALY to 474,935SEK/QALY in sensitivity and variability analyses. CONCLUSIONS: The results suggest etravirine to be cost-effective in Sweden when added to a standard multi-drug regimen in pretreated HIV patients with evidence of NNRTI and PI resistance.