BACKGROUND The use of boosted protease inhibitor (PI)-based antiretroviral therapy has become increasingly recommended in international HIV treatment consensus guidelines based on the results of randomized clinical trials. However, the impact of this new treatment strategy has not yet been evaluated in community-treated cohorts. METHODS We evaluated baseline characteristics and plasma HIV RNA responses to unboosted and boosted PI-based highly active antiretroviral therapy (HAART) among antiretroviral-naïve HIV-infected patients in British Columbia, Canada who initiated HAART between August 1997 and September 2003 and who were followed until September 2004. We evaluated time to HIV-1 RNA suppression (<500 HIV-1 RNA copies/mL) and HIV-1 RNA rebound (>or=500 copies/mL), while stratifying patients into those that received boosted and unboosted PI-based HAART as the initial regimen, using Kaplan-Meier methods and Cox proportional hazards regression. RESULTS During the study period, 682 patients initiated therapy with unboosted PI and 320 individuals initiated HAART with a boosted PI. Those who initiated therapy with a boosted PI were more likely to have a CD4 cell count <200 cells/muL and to have a plasma HIV RNA>100 000 copies/mL, and to have AIDS at baseline (all P<0.001). However, when we examined virological response rates, those who initiated HAART with a boosted PI achieved more rapid virological suppression [relative hazard 1.26, 95% confidence interval (CI) 1.06-1.51, P=0.010]. CONCLUSIONS Patients prescribed boosted PIs achieved superior virological response rates despite baseline factors that have been associated with inferior virological responses to HAART. Despite the inherent limitations of observational studies which require this study be interpreted with caution, these findings support the use of boosted PIs for initial HAART therapy.