PMID- 26379163
OWN - NLM
STAT- MEDLINE
DCOM- 20161017
LR  - 20201209
IS  - 1532-0987 (Electronic)
IS  - 0891-3668 (Linking)
VI  - 34
IP  - 12
DP  - 2015 Dec
TI  - Efavirenz Capsule Sprinkle and Liquid Formulations With Didanosine and 
      Emtricitabine in HIV-1-infected Infants and Children 3 Months to 6 Years of Age: 
      Study AI266-922.
PG  - 1355-60
LID - 10.1097/INF.0000000000000913 [doi]
AB  - BACKGROUND: AI266-922 was an open-label, dose-ranging study that assessed the 
      pharmacokinetics, safety and efficacy of efavirenz (EFV) in children (3 months to 
      6 years). METHODS: Antiretroviral-naive and antiretroviral-experienced 
      HIV-1-infected children received once-daily EFV as oral solution or capsule 
      sprinkle plus didanosine and emtricitabine (FTC). Pharmacokinetic analyses were 
      undertaken at week 2 and repeated at weeks 10 and 18 after an EFV dose change or 
      switch from oral solution to capsule sprinkle. RESULTS: Thirty-seven subjects 
      were treated. EFV area under the plasma concentration-time curve over 1 dosing 
      interval from time 0 to 24 hours postdose values were generally suboptimal (<110 
      muM x h) in subjects younger than 3 years treated with oral solution; these 
      subjects switched to capsule sprinkle. Twenty of 21 subjects younger than 3 years 
      treated with capsule sprinkle achieved an EFV area under the plasma 
      concentration-time curve over 1 dosing interval from time 0 to 24 hours postdose 
      value >110 muM x h, although higher initial doses were administered in this age 
      group. Interpatient variability in EFV exposure was high. By week 48, 77.8% and 
      63.0% of subjects achieved HIV-RNA <400 and <50 copies/mL, respectively. Median 
      changes in log10 HIV-RNA and CD4 percentage from baseline were -3.18 copies/mL 
      and +6%, respectively. Two (5.4%) patients discontinued because of adverse events 
      (AEs). Serious AEs occurred in 20 (54.1%) subjects. Common AEs were diarrhea 
      (49%), nasopharyngitis (35%) and pneumonia (30%). Overall, 43% of subjects with 
      suboptimal EFV exposure at week 2 developed resistance. CONCLUSIONS: Once-daily 
      EFV, given as capsule sprinkle, achieved target exposures in this study although 
      doses were 2-3 times higher than Food and Drug Administration-approved doses for 
      children younger than 3 years. These data are useful for dose selection modeling 
      and simulation; however, Food and Drug Administration-approved doses should be 
      used clinically. EFV + didanosine + FTC was efficacious with no new pediatric 
      safety findings reported.
FAU - Pavia-Ruz, Noris
AU  - Pavia-Ruz N
AD  - From the *Hospital Infantil de Mexico Federico Gomez, Mexico City, Mexico; 
      daggerFamily Clinical Research Unit, Tyberberg Children's Hospital, Cape Town, South 
      Africa; double daggerUniversidad Panama School of Medicine, Hospital del Nino de Panama, 
      Panama City, Panama;  section signHIV Netherlands Australia Thailand Research Collaboration 
      (HIV-NAT), Thai Red Cross AIDS Research Centre (TRCARC), Bangkok, Thailand; 
       paragraph signBristol-Myers Squibb, Wallingford, Connecticut;  ||Bristol-Myers Squibb, Hopewell, 
      New Jersey; and **Bristol-Myers Squibb, Plainsboro, New Jersey.
FAU - Rossouw, Magdel
AU  - Rossouw M
FAU - Saez-Llorens, Xavier
AU  - Saez-Llorens X
FAU - Bunupuradah, Torsak
AU  - Bunupuradah T
FAU - Taylor, Mathew
AU  - Taylor M
FAU - Yang, Rong
AU  - Yang R
FAU - Sevinsky, Heather
AU  - Sevinsky H
FAU - Krystal, Mark
AU  - Krystal M
FAU - Lataillade, Max
AU  - Lataillade M
FAU - Seekins, Daniel
AU  - Seekins D
FAU - Biguenet, Sophie
AU  - Biguenet S
LA  - eng
SI  - ClinicalTrials.gov/NCT00364793
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PL  - United States
TA  - Pediatr Infect Dis J
JT  - The Pediatric infectious disease journal
JID - 8701858
RN  - 0 (Alkynes)
RN  - 0 (Benzoxazines)
RN  - 0 (Cyclopropanes)
RN  - G70B4ETF4S (Emtricitabine)
RN  - JE6H2O27P8 (efavirenz)
RN  - K3GDH6OH08 (Didanosine)
SB  - IM
MH  - Alkynes
MH  - Benzoxazines/administration & dosage/pharmacokinetics/*therapeutic use
MH  - Child, Preschool
MH  - Cyclopropanes
MH  - Didanosine/administration & dosage/pharmacokinetics/*therapeutic use
MH  - Emtricitabine/administration & dosage/pharmacokinetics/*therapeutic use
MH  - Female
MH  - HIV Infections/*drug therapy/epidemiology
MH  - Humans
MH  - Infant
MH  - Male
MH  - Prospective Studies
EDAT- 2015/09/18 06:00
MHDA- 2016/10/19 06:00
CRDT- 2015/09/18 06:00
PHST- 2015/09/18 06:00 [entrez]
PHST- 2015/09/18 06:00 [pubmed]
PHST- 2016/10/19 06:00 [medline]
AID - 10.1097/INF.0000000000000913 [doi]
PST - ppublish
SO  - Pediatr Infect Dis J. 2015 Dec;34(12):1355-60. doi: 10.1097/INF.0000000000000913.