title: 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.
abstract: 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.
authors.affiliation: 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.
authors.forename: Xavier
authors.initials: X
authors.lastname: Saez-Llorens
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Castaño
authors.forename: Mobeen
authors.initials: M
authors.lastname: Rathore
authors.forename: Joseph
authors.initials: J
authors.lastname: Church
authors.forename: Jaime
authors.initials: J
authors.lastname: Deville
authors.forename: Aditya
authors.initials: A
authors.lastname: Gaur
authors.forename: Dora
authors.initials: D
authors.lastname: Estripeaut
authors.forename: Kirsten
authors.initials: K
authors.lastname: White
authors.forename: Sarah
authors.initials: S
authors.lastname: Arterburn
authors.forename: Jeffrey V
authors.initials: JV
authors.lastname: Enejosa
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Cheng
authors.forename: Steven L
authors.initials: SL
authors.lastname: Chuck
authors.forename: Martin S
authors.initials: MS
authors.lastname: Rhee
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D018119:Stavudine / Q000009:adverse effects / Q000627:therapeutic use*; D000068698:Tenofovir; D016896:Treatment Outcome; D019562:Viral Load; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D012367:RNA, Viral; D015215:Zidovudine; D000068698:Tenofovir; D018119:Stavudine; D000225:Adenine