Background:  Decreased bone mineral density (BMD) has been associated to the use of tenofovir DF (TDF)  in HIV-infected adults receiving highly active antiretroviral therapy (HAART). Data in children are conflicting. The aim of this study was to assess the safety of a TDF-containing HAART on bone health in a cohort of pediatric patients.

Methods:  This was a single-site, longitudinal, controlled, observational study. We enrolled 21 vertically HIV-infected Caucasian youths (11 girls), aged 4.9 to 17.9 years, with undetectable viral load, receiving HAART containing lamivudine, stavudine (d4T) and a protease inhibitor (PI). At enrollment, all subjects replaced d4T with TDF and PI with efavirenz (EFV). We also studied 194 healthy youths (90 girls), aged 4.9 to 21.9 years. At baseline, 12, 24, 36, 48, and 60 months, we measured BMD at the lumbar spine and in the whole skeleton by dual-energy x-ray absorptiometry, serum bone alkaline phosphatase (BAP), and urinary N-telopeptide of type-I collagen (NTx). Expected BMD and bone metabolism values were computed from data of healthy controls (HC); comparison was made by Wilcoxon test. Z-scores for BMD and bone metabolism values were also computed and their changes over time assessed by ANOVA.

Results:  During the study period, patients were on average shorter and lighter than age- and sex- matched HC, maintained HIV/RNA <50 copies/mL and stable CD4⁺ count: mean values (range) at baseline vs 60-month were 842 (236 to 1518) and 854 (314 to 1526) cells/μL, respectively. In comparison to the expected values, patients’ BMD at the lumbar spine was significantly lower at baseline and after 12 and 24 months (P =0.02; P =0.01; and P =0.02, respectively). No differences were observed at 36, 48, and 60 months after switching. Patients’ total body BMD compared to the expected values was significantly lower at baseline, 12, 24, 48, and 60 months (P =0.033; P =0.05; P =0.028; P =0.015; and P =0.006, respectively). Patients’ BMD z-score at the lumbar spine and in total body did not changed significantly over time. Serum BAP and urinary NTx concentrations were higher than expected at baseline, and they remained significantly higher during the study period. BAP and NTx z-scores did not changed significantly over time.

Conclusions:  Through month 60, switching d4T to TDF and PI to EFV in HIV-infected youths, maintains an optimal control of infection, does not normalize bone mass and metabolism, but is not associated with a further impairment of these parameters.