Pharmacokinetics, safety and efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in children with HIV aged from 2 years and weighing at least 14 kg

IF 4.6 1区医学 Q2 IMMUNOLOGY

Journal of the International AIDS Society Pub Date : 2025-01-30 DOI:10.1002/jia2.26414

Eva Natukunda, Aditya H. Gaur, Pope Kosalaraksa, Elizabeth Hellström, Renate Strehlau, Afaaf Liberty, Stephanie Cox, Rory Leisegang, Ramesh Palaparthy, Susanne Crowe, Vinicius Vieira, Kathryn Kersey, Natella Rakhmanina

{"title":"Pharmacokinetics, safety and efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in children with HIV aged from 2 years and weighing at least 14 kg","authors":"Eva Natukunda, Aditya H. Gaur, Pope Kosalaraksa, Elizabeth Hellström, Renate Strehlau, Afaaf Liberty, Stephanie Cox, Rory Leisegang, Ramesh Palaparthy, Susanne Crowe, Vinicius Vieira, Kathryn Kersey, Natella Rakhmanina","doi":"10.1002/jia2.26414","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Introduction</h3>\n \n <p>Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) was efficacious and well tolerated in children/adolescents with HIV (aged ≥6 years, weighing ≥25 kg) in a Phase 2/3 study. Here, we report data from children aged ≥2 years and weighing ≥14–<25 kg.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>This is an analysis of data from the youngest cohort in an open-label, multicentre, multi-cohort, single-group, international study of children/adolescents with HIV. Participants in this cohort were children aged ≥2 years, weighing ≥14–<25 kg at screening and able to swallow tablets, on stable antiretroviral therapy with virologic suppression (HIV-1 RNA <50 copies/ml for ≥6 consecutive months) and a CD4 count ≥400 cells/µl. Eligible participants received low-dose E/C/F/TAF (90/90/120/6 mg) once daily through Week 48. The study included pharmacokinetic evaluation of the low-dose E/C/F/TAF tablet at Week 2. Safety, efficacy, palatability and acceptability were also evaluated.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Between 16 January and 25 November 2019, 27 participants were enrolled with a median (quartile [Q]1, Q3) age of 6 (4, 8) years, body weight of 19.3 (17.0, 20.5) kg, CD4 count of 1061 (895, 1315) cells/µl and CD4 cell percentage of 37.4 (30.6, 40.3). Most (92.6%) participants acquired HIV through vertical transmission. On 6 October 2020 (data-cut), median (Q1, Q3) exposure to E/C/F/TAF was 48.3 (48.0, 60.1) weeks. Pharmacokinetic parameters were within the safe and efficacious range of previous data in adult and paediatric populations. Drug-related treatment-emergent adverse events occurred in 4/27 (15%) participants. There were no Grade 3/4 adverse events, or adverse events leading to E/C/F/TAF discontinuation. One participant experienced a serious treatment-emergent adverse event (Grade 2 pneumonia not considered E/C/F/TAF related). Virologic suppression (US FDA Snapshot algorithm) was maintained by 26/27 (96%) participants at Weeks 24 and 48. At Week 48, most children reported positive palatability (84.6%) and acceptability (96.2%).</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>These data support the use of single-tablet E/C/F/TAF (90/90/120/6 mg) regimen for the treatment of HIV in children aged ≥2 years and weighing ≥14–<25 kg.</p>\n </section>\n \n <section>\n \n <h3> Clinical Trial Number</h3>\n \n <p>NCT01854775</p>\n </section>\n </div>","PeriodicalId":201,"journal":{"name":"Journal of the International AIDS Society","volume":"28 2","pages":""},"PeriodicalIF":4.6000,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782835/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the International AIDS Society","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jia2.26414","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) was efficacious and well tolerated in children/adolescents with HIV (aged ≥6 years, weighing ≥25 kg) in a Phase 2/3 study. Here, we report data from children aged ≥2 years and weighing ≥14–<25 kg.

Methods

This is an analysis of data from the youngest cohort in an open-label, multicentre, multi-cohort, single-group, international study of children/adolescents with HIV. Participants in this cohort were children aged ≥2 years, weighing ≥14–<25 kg at screening and able to swallow tablets, on stable antiretroviral therapy with virologic suppression (HIV-1 RNA <50 copies/ml for ≥6 consecutive months) and a CD4 count ≥400 cells/µl. Eligible participants received low-dose E/C/F/TAF (90/90/120/6 mg) once daily through Week 48. The study included pharmacokinetic evaluation of the low-dose E/C/F/TAF tablet at Week 2. Safety, efficacy, palatability and acceptability were also evaluated.

Results

Between 16 January and 25 November 2019, 27 participants were enrolled with a median (quartile [Q]1, Q3) age of 6 (4, 8) years, body weight of 19.3 (17.0, 20.5) kg, CD4 count of 1061 (895, 1315) cells/µl and CD4 cell percentage of 37.4 (30.6, 40.3). Most (92.6%) participants acquired HIV through vertical transmission. On 6 October 2020 (data-cut), median (Q1, Q3) exposure to E/C/F/TAF was 48.3 (48.0, 60.1) weeks. Pharmacokinetic parameters were within the safe and efficacious range of previous data in adult and paediatric populations. Drug-related treatment-emergent adverse events occurred in 4/27 (15%) participants. There were no Grade 3/4 adverse events, or adverse events leading to E/C/F/TAF discontinuation. One participant experienced a serious treatment-emergent adverse event (Grade 2 pneumonia not considered E/C/F/TAF related). Virologic suppression (US FDA Snapshot algorithm) was maintained by 26/27 (96%) participants at Weeks 24 and 48. At Week 48, most children reported positive palatability (84.6%) and acceptability (96.2%).

Conclusions

These data support the use of single-tablet E/C/F/TAF (90/90/120/6 mg) regimen for the treatment of HIV in children aged ≥2 years and weighing ≥14–<25 kg.

Clinical Trial Number

NCT01854775

查看原文本刊更多论文

依维替韦/可比司他/恩曲他滨/替诺福韦阿拉芬胺在2岁以上体重至少14公斤的艾滋病毒感染儿童中的药代动力学、安全性和有效性

在一项2/3期研究中，Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide （E/C/F/TAF）对儿童/青少年HIV感染者（年龄≥6岁，体重≥25 kg）有效且耐受性良好。在这里，我们报告了年龄≥2岁、体重≥14岁儿童的数据。方法：这是一项开放标签、多中心、多队列、单组、国际艾滋病儿童/青少年研究中最年轻队列的数据分析。结果：在2019年1月16日至11月25日期间，27名参与者入组，中位年龄（四分位数[Q]1， Q3）为6（4,8）岁，体重为19.3 (17.0,20.5)kg， CD4计数为1061（895,1315）个细胞/µl， CD4细胞百分比为37.4（30.6,40.3）。大多数（92.6%）参与者通过垂直传播感染艾滋病毒。2020年10月6日（数据删除），E/C/F/TAF暴露的中位数（第一季度、第三季度）为48.3周（48.0周、60.1周）。在成人和儿童人群中，药代动力学参数在先前数据的安全有效范围内。4/27（15%）参与者出现药物相关治疗不良事件。没有3/4级不良事件，也没有导致E/C/F/TAF停药的不良事件。1名参与者出现了严重的治疗不良事件（2级肺炎，与E/C/F/TAF无关）。在第24周和第48周，26/27（96%）的参与者保持病毒学抑制（美国FDA快照算法）。在第48周，大多数儿童报告了积极的适口性（84.6%）和可接受性（96.2%）。结论：这些数据支持E/C/F/TAF单片（90/90/120/6 mg）方案治疗年龄≥2岁、体重≥14岁儿童HIV。临床试验编号：NCT01854775。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of the International AIDS Society IMMUNOLOGY-INFECTIOUS DISEASES

CiteScore

8.60

自引率

10.00%

发文量

186

审稿时长

>12 weeks

期刊介绍： The Journal of the International AIDS Society (JIAS) is a peer-reviewed and Open Access journal for the generation and dissemination of evidence from a wide range of disciplines: basic and biomedical sciences; behavioural sciences; epidemiology; clinical sciences; health economics and health policy; operations research and implementation sciences; and social sciences and humanities. Submission of HIV research carried out in low- and middle-income countries is strongly encouraged.