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A Randomized, Open-Label Study of the Safety and Efficacy of Switching Stavudine or Zidovudine to Tenofovir Disoproxil Fumarate in HIV-1–infected Children With Virologic Suppression

Saez-Llorens, Xavier MD*; Castaño, Elizabeth MD*; Rathore, Mobeen MD; Church, Joseph MD; Deville, Jaime MD§; Gaur, Aditya MD; Estripeaut, Dora MD*; White, Kirsten PhD; Arterburn, Sarah MS; Enejosa, Jeffrey V. MD**; Cheng, Andrew K. MD, PhD; Chuck, Steven L. MD; Rhee, Martin S. MD

Pediatric Infectious Disease Journal: April 2015 - Volume 34 - Issue 4 - p 376–382
doi: 10.1097/INF.0000000000000289
HIV Reports

Background: The safety and efficacy of tenofovir disoproxil fumarate (TDF) in HIV-1–infected children have not been evaluated in a randomized controlled trial.

Methods: Subjects (2 to <16 years) on a stavudine (d4T) or zidovudine (ZDV) containing regimen with HIV-1 RNA <400 copies/mL were randomized to either switch d4T or ZDV to TDF or continue d4T or ZDV. The primary endpoint was the proportion of subjects with HIV-1 RNA < 400 copies/mL at Week 48 with a prespecified noninferiority margin of 15%. After the 48-week randomized phase, eligible subjects were rolled over to an extension phase.

Results: Ninety-seven children (48 TDF vs. 49 d4T or ZDV) were randomized and treated. The percent of subjects who maintained virologic suppression in the TDF versus d4T or ZDV group at Week 24 were 93.8% versus 89.8% (difference 4.0%; 95% confidence interval:: −6.9% to 14.9%) and at Week 48 were 83.3% versus 91.8% (difference: −8.5%; 95% confidence interval: −21.5% to 4.5%; missing = failure, intent-to-treat analysis). No subjects discontinued study drug because of an adverse event in the 48 weeks of randomized phase. Four subjects discontinued TDF because of proximal renal tubulopathy in the extension phase.

Conclusions: Our study did not demonstrate noninferiority of TDF versus d4T or ZDV at Week 48. Overall safety and tolerability of TDF in children were consistent with adults. TDF may be considered as an alternative to d4T or ZDV in HIV-infected children.

From the *Department of Infectious Diseases, Hospital del Niño, Panama City, Panama; Division of Pediatric Infectious Disease and Immunology, University of Florida Health Science Center, Jacksonville, FL; Division of Clinical Immunology and Allergy, Children’s Hospital Los Angeles; §Division of Pediatric Infectious Diseases, University of California in Los Angeles, Los Angeles, CA; Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN; Gilead Sciences Inc., Foster City; and **Dynavax Technologies, Berkley, CA.

Accepted for publication December 13, 2013.

Trial registration: GS-US-104–0352 is registered with ClinicalTrials.gov (NCT00528957).

All study investigators received research funding from Gilead Sciences to support their subjects’ participation in this study. J.V.E. and S.L.C. were previous employees and K.W., S.A., A.K.C. and M.S.R. are current employees of the study sponsor, Gilead Sciences Inc. and own its stocks and/or stock options. The authors have no other funding or conflicts of interest to disclose.

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Address for correspondence: Martin S. Rhee, MD, 333 Lakeside Drive, Foster City, CA 94404. E-mail: mrhee@gilead.com.

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