Longitudinal Evaluation of Bone Safety in Children and Adolescents With HIV-1 Starting Tenofovir Alafenamide-Containing Antiretroviral Therapy - PubMed (original) (raw)

Clinical Trial

. 2025 Aug 7;14(7):piaf062.

doi: 10.1093/jpids/piaf062.

Aditya H Gaur 2, Jaime Gerardo Deville 3, Pope Kosalaraksa 4, Renate Strehlau 5, Elizabeth Castaño 6, Afaaf Liberty 7, Susanne Crowe 8, Ramesh Palaparthy 9, Vinicius Adriano Vieira 10, Kathryn Kersey 11, Natella Rakhmanina 12 13 14, Catherine M Gordon 15

Affiliations

Clinical Trial

Longitudinal Evaluation of Bone Safety in Children and Adolescents With HIV-1 Starting Tenofovir Alafenamide-Containing Antiretroviral Therapy

Eva Natukunda et al. J Pediatric Infect Dis Soc. 2025.

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 2 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 to < 18 years, weighing ≥ 35 kg), group 2 (aged 6 to < 12 years, weighing ≥ 25 kg), and group 3 (aged ≥ 2 years, weighing 14 to < 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 groups 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.

Keywords: Human immunodeficiency virus; antiretroviral therapy; bone health; pediatric; tenofovir alafenamide.

Plain language summary

This pooled analysis of 2 phase 2/3 studies demonstrated acceptable bone safety of TAF-based regimens in children and adolescents with HIV-1 over medium- to long-term exposure (median: 168.3-320.3 weeks). Bone mineral density increased over time and was consistent with developmental stage.

© The Author(s) 2025. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society.

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Conflict of interest statement

A.G. reports research grants from Gilead Sciences, Inc. and ViiV Healthcare, payments for expert advisory board participation and serving as a webinar panelist from ViiV Healthcare. J.G.D. and P.K. report research funding paid to their institution from Gilead Sciences, Inc. R.S. reports research funding paid to their institution from Gilead Sciences, Inc., GSK, Merck, and Penta; consulting fees from GSK and ViiV Healthcare; and travel support from Enanta Pharmaceuticals and Gilead Sciences, Inc. S.C. is an employee of Gilead Sciences, Inc., and holds stocks/shares in Alcon, Gilead Sciences, Inc., Novartis, and Sandoz. R.P., V.A.V., and K.K. are employees of and hold stock in Gilead Sciences, Inc. N.R. reports research funding paid to their institution from Gilead Sciences, Inc., GSK, Merck, and Penta; travel support from Gilead Sciences, Inc.; and payments for expert advisory boards and expert testimony from ViiV Healthcare. C.M.G. reports serving as a paid consultant for Gilead Sciences, Inc., while employed at Baylor College of Medicine. The opinions expressed in this article are the author’s own and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government.

Figures

Figure 1

Figure 1

Change From Baseline in BMD Over Time for Spine (A) and TBLH (B) (Spine and TBLH DXA Analysis Sets). For all analyses, participants were grouped based on their age/weight at screening. BL, baseline; BMD, bone mineral density; DXA, dual-energy X-ray absorptiometry; TBLH, total body less head; Q, quartile.

Figure 2

Figure 2

Change From Baseline in HAZ-Adjusted BMD Z-Scores Over Time for Spine (A) and TBLH (B) (Spine and TBLH DXA Analysis Sets). For all analyses, participants were grouped based on their age/weight at screening. BL, baseline; BMD, bone mineral density; DXA, dual-energy X-ray absorptiometry; HAZ, height-for-age Z-score; TBLH, total body less head; Q, quartile.

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