Differential skeletal impact of tenofovir disoproxil fumarate in young versus old hiv-infected adults

Abstract

Background: Lower peak bone mass in early adulthood predicts subsequent fragility fractures. Antiretroviral toxicity could contribute to young HIV-infected individuals not achieving adequate peak bone mass. Objective: To determine if tenofovir disoproxil fumarate’s (TDF) effect on bone mineral density (BMD) differs by age. Methods: We examined BMD data at the lumbar spine and hip from AIDS Clinical Trials Group (ACTG) A5224s and ASSERT and randomized treatment-naive studies comparing TDF/emtricitabine versus abacavir/lamivudine (with efavirenz or atazanavir/ritonavir). In this post hoc analysis,we defined the TDF effect as the difference between mean 48-week BMD per cent changes for lumbar spine and hip in individuals randomized to TDF versus abacavir. We used multivariable linear regression to compare the TDF effect in individuals younger and older than 30 years. If TDF effect by age did not differ significantly between studies, we pooled study populations. Otherwise, analyses were conducted separately within each study population. Results: Among 652 subjects, 21% were below age 30 years. The relationship between age and TDF effect significantly differed between A5224s and ASSERT (P=0.008 for lumbar spine; P=0.007 for hip). In A5224s, there was more bone loss with TDF at lumbar spine and hip in subjects under 30 years old versus in older subjects (–4.5% vs –1.4%; P=0.045; –4.3% vs –1.6%; P50.026, respectively). There was no significant evidence for this age-associated TDF effect in ASSERT. Conclusions: Therewas heterogeneity in the observed effect of TDF on bone density in young adults compared to older adults, suggesting that further investigation is required to understand the impact of age onBMDdecline with TDF.