title: 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.
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 > or = 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 microL (17%), which increased at week 96 by a median of +329 cells per microL (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.
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Box 3461, Durham, NC 27710, USA. ross.mckinney@duke.edu
authors.forename: Ross E
authors.initials: RE
authors.lastname: McKinney
authors.forename: John
authors.initials: J
authors.lastname: Rodman
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Hu
authors.forename: Paula
authors.initials: P
authors.lastname: Britto
authors.forename: Michael
authors.initials: M
authors.lastname: Hughes
authors.forename: Mary Elizabeth
authors.initials: ME
authors.lastname: Smith
authors.forename: Leslie K
authors.initials: LK
authors.lastname: Serchuck
authors.forename: Joyce
authors.initials: J
authors.lastname: Kraimer
authors.forename: Alberto A
authors.initials: AA
authors.lastname: Ortiz
authors.forename: Patricia
authors.initials: P
authors.lastname: Flynn
authors.forename: Ram
authors.initials: R
authors.lastname: Yogev
authors.forename: Stephen
authors.initials: S
authors.lastname: Spector
authors.forename: Linda
authors.initials: L
authors.lastname: Draper
authors.forename: Paul
authors.initials: P
authors.lastname: Tran
authors.forename: Melissa
authors.initials: M
authors.lastname: Scites
authors.forename: Ruth
authors.initials: R
authors.lastname: Dickover
authors.forename: Adriana
authors.initials: A
authors.lastname: Weinberg
authors.forename: Coleen
authors.initials: C
authors.lastname: Cunningham
authors.forename: Elaine
authors.initials: E
authors.lastname: Abrams
authors.forename: M Robert
authors.initials: MR
authors.lastname: Blum
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Chittick
authors.forename: Laurie
authors.initials: L
authors.lastname: Reynolds
authors.forename: Mobeen
authors.initials: M
authors.lastname: Rathore
mesh_terms: D000293:Adolescent; D000328:Adult; D000480:Alkynes; D048588:Benzoxazines / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D002985:Clinical Protocols; D003521:Cyclopropanes; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016049:Didanosine / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D000068679:Emtricitabine; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D013995:Time
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D003841:Deoxycytidine; D000068679:Emtricitabine; C098320:efavirenz; D016049:Didanosine