对开始使用含替诺福韦艾拉酚胺抗逆转录病毒疗法的HIV-1感染儿童和青少年进行骨骼安全性的纵向评估。

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

作者信息

Natukunda Eva, Gaur Aditya H, Deville Jaime Gerardo, Kosalaraksa Pope, Strehlau Renate, Castaño Elizabeth, Liberty Afaaf, Crowe Susanne, Palaparthy Ramesh, Vieira Vinicius Adriano, Kersey Kathryn, Rakhmanina Natella, Gordon Catherine M

机构信息

Department of Pediatrics, Joint Clinical Research Centre, Kampala, Uganda.

Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, United States.

出版信息

J Pediatric Infect Dis Soc. 2025 Aug 7;14(7). doi: 10.1093/jpids/piaf062.

DOI:10.1093/jpids/piaf062

PMID:40632108

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12343092/

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.

摘要

背景

在临床试验中，服用替诺福韦艾拉酚胺（TAF）的成年参与者的骨骼安全性优于服用富马酸替诺福韦二吡呋酯的参与者。在此，我们报告含TAF方案对感染人类免疫缺陷病毒（HIV）的儿童和青少年骨骼健康的中长期影响。

方法

对两项2/3期临床研究（NCT01854775和NCT02285114）的数据进行事后汇总分析，评估基于TAF的方案在HIV-1感染儿童和青少年中的药代动力学、安全性和疗效。参与者分为1组（年龄12至<18岁，体重≥35kg）、2组（年龄6至<12岁，体重≥25kg）和3组（年龄≥2岁，体重14至<25kg）。评估包括病毒学抑制、身高Z评分、坦纳分期、脊柱和全身除头部外（TBLH；两者的绝对值以及按年龄调整身高Z评分[HAZ调整]）的骨矿物质密度（BMD）、骨血清标志物、与骨相关的不良事件以及药代动力学评估。

结果

总体而言，共纳入169名参与者并接受治疗（1组78名，2组61名，3组30名）。1组、2组和3组参与者接受研究药物的中位（范围）暴露时间分别为320.3（8.3 - 492.3）、290.1（24.0 - 393.9）和168.3（9.0 - 193.0）周。所有组的病毒学抑制（HIV-1 RNA<50拷贝/mL）率都很高。所有组的脊柱和TBLH绝对BMD随时间增加，所有组的脊柱和TBLH HAZ调整BMD Z评分增加或保持稳定。骨血清标志物无显著变化，也没有与治疗相关的骨折或与骨相关的不良事件。