The efficacy of boosted protease inhibitor monotherapy (BPIm) in HIV-positive patients with complex medical problems was assessed in ten patients. With BPIm, median (range) HIV viral load reduction was log10 2.15 (1.62-3.1) by 4-8 weeks; in four patients, viral load was < 400 copies/ml. During follow-up, at median (range) = 50 (8-156) weeks, no patient had an opportunistic illness; one patient developed new PI mutations after 48 weeks. These very preliminary data need further confirmation on a larger scale. © 2007 Lippincott Williams & Wilkins, Inc.