Longitudinal evaluation of bone safety in children and adolescents with HIV-1 starting tenofovir alafenamide-containing antiretroviral therapy.

Abstract

Background: Adult participants taking tenofovir alafenamide (TAF) in clinical trials had a better bone safety profile than those taking tenofovir disoproxil fumarate. Herein, we report medium- to long-term effects of TAF-containing regimens on bone health in children and adolescents with human immunodeficiency virus (HIV).

Methods: This post hoc pooled analysis of data from two phase 2/3 clinical studies (NCT01854775 and NCT02285114) evaluated the pharmacokinetics, safety, and efficacy of TAF-based regimens in children and adolescents with HIV-1. Participants were categorized into Group 1 (aged 12-<18 years, weighing ≥35 kg), Group 2 (aged 6-<12 years, weighing ≥25 kg), and Group 3 (aged ≥2 years, weighing 14-<25 kg). Evaluations included virologic suppression, height Z-score, Tanner stage, bone mineral density (BMD) of the spine and total body less head (TBLH; absolute and height-for-age Z-score adjusted [HAZ-adjusted] for both), bone serum markers, bone-related adverse events, and pharmacokinetic assessments.

Results: Overall, 169 participants were enrolled and treated (78, 61, and 30 in Group 1, 2, and 3, respectively). Median (range) exposure to study drug was 320.3 (8.3-492.3), 290.1 (24.0-393.9), and 168.3 (9.0-193.0) weeks in Groups 1, 2, and 3, respectively. Virologic suppression (HIV-1 RNA <50 copies/mL) rates were high across all groups. Spine and TBLH absolute BMD increased over time in all groups, and spine and TBLH HAZ-adjusted BMD Z-scores increased or remained stable in all groups. There were no significant changes in bone serum markers, and no treatment-related fractures or bone-related adverse events.

Conclusions: TAF-based regimens demonstrated acceptable medium- to long-term bone safety in children and adolescents with HIV.