Low bone mineral density with tenofovir: does statistically significant mean clinically significant?

Adults with human immunodeficiency (HIV) infection appear to have a greater prevalence of low bone mineral density (BMD) and of fractures than do adults without HIV infection [1,2]. HIV infection itself may contribute to this greater prevalence. HIV induces inflammation (a known association with accelerated BMD loss), and low BMD has been reported in individuals with untreated HIV infection [1, 3]. The use of particular antiretroviral drugs appears to be a contributing factor. Of those drugs that are in common use today, the nucleotide reverse-transcriptase inhibitor tenofovir and various HIV protease inhibitors have been shown to lower BMD in randomized trials [4, 5]. Furthermore, BMD was found to increase initially with cessation of antiretroviral therapy, relative to BMD in patients with continuous therapy [6]. In a randomized, placebo-controlled trial, the ASSERT investigators assigned antiretroviral-naive adults to commence efavirenz therapy in combination with te-