Long-term Safety and Efficacy of a Once-Daily Regimen of Emtricitabine, Didanosine, and Efavirenz in HIV-Infected, Therapy-Naive Children and Adolescents: Pediatric AIDS Clinical Trials Group Protocol P1021

Author:

McKinney Ross E.1,Rodman John2,Hu Chengcheng3,Britto Paula3,Hughes Michael3,Smith Mary Elizabeth4,Serchuck Leslie K.5,Kraimer Joyce6,Ortiz Alberto A.6,Flynn Patricia2,Yogev Ram7,Spector Stephen8,Draper Linda9,Tran Paul4,Scites Melissa10,Dickover Ruth11,Weinberg Adriana12,Cunningham Coleen13,Abrams Elaine14,Blum M. Robert15,Chittick Gregory E.15,Reynolds Laurie16,Rathore Mobeen10,

Affiliation:

1. Department of Pediatrics, Duke University Medical Center, Durham, North Carolina

2. Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, Tennessee

3. Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts

4. Division of AIDS, National Institute of Allergy and Infectious Diseases

5. Pediatric, Adolescent, and Maternal AIDS Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland

6. Social & Scientific Systems, Inc, Silver Spring, Maryland

7. Department of Pediatrics, Children's Memorial Hospital, Chicago, Illinois

8. Department of Pediatrics, University of California, San Diego, California

9. Frontier Science and Technology Research Foundation, Amherst, New York

10. Department of Pediatrics, University of Florida Health Science Center, Jacksonville, Florida

11. Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, California

12. Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado

13. Department of Pediatrics, State University of New York Health Science Center, Syracuse, New York

14. Department of Pediatrics, Harlem Hospital, New York, New York

15. Gilead Sciences, Inc, Durham, North Carolina

16. Bristol-Myers Squibb Company, Wallingford, Connecticut

Abstract

BACKGROUND. Compliance with complex antiretroviral therapy regimens is a problem for HIV-1–infected children and their families. Simple, safe, and effective regimens are important for long-term therapeutic success. METHODS. A novel, once-daily dosing regimen of 3 antiretroviral drugs, emtricitabine, didanosine, and efavirenz, was tested in 37 therapy-naive HIV-infected children and adolescents between 3 and 21 years of age (inclusive). Subjects were followed for ≥96 weeks on an intention-to-treat basis. Signs, symptoms, plasma HIV-1 RNA viral load, CD4 counts, and safety laboratories were followed regularly. End points were the proportion of subjects with plasma HIV <400 or 50 HIV copies per mL and safety and tolerability of the regimen. RESULTS. Thirty-seven subjects enrolled at 16 sites. Two subjects with rashes during the first 2 weeks of therapy were the only adverse events leading to study-drug discontinuation. Other early (before protocol-scheduled conclusion) study discontinuations included 3 viral failures on treatment and 5 patients who stopped therapy for apparently nonmedical reasons. Possible drug-related adverse events included 1 grade 4 low-glucose and 5 varied grade 3 events. There were no deaths. Virologic outcomes demonstrated that 32 (85%) of 37 subjects achieved viral suppression to <400 RNA copies per mL, and 26 (72%) of 37 subjects maintained sustained suppression at <50 copies per mL through week 96. The median baseline CD4 count was 310 per μL (17%), which increased at week 96 by a median of +329 cells per μL (by +18% CD4). Pharmacokinetic results were as predicted for emtricitabine, didanosine, and efavirenz capsules, whereas efavirenz concentrations in children receiving efavirenz oral solution were lower than anticipated, requiring a dose escalation after the planned assessment point. CONCLUSIONS. A once-daily regimen of emtricitabine, didanosine, and efavirenz proved to be safe and tolerable and demonstrated good immunologic and virologic efficacy in this 2-year study.

Publisher

American Academy of Pediatrics (AAP)

Subject

Pediatrics, Perinatology and Child Health

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3