Atazanavir and atazanavir/ritonavir pharmacokinetics in HIV-infected infants, children, and adolescents

AIDS. 2011 Jul 31;25(12):1489-96. doi: 10.1097/QAD.0b013e328348fc41.


Objective: To describe the pharmacokinetics of atazanavir (ATV) and ritonavir-boosted ATV (ATV/r) in children aged 91 days to 21 years.

Design: A phase I/II, open-label, multicenter study of once-daily ATV and ATV/r as part of combination antiretroviral treatment in HIV-infected treatment-experienced and treatment-naive children.

Setting: Sites in the United States and South Africa.

Participants: One hundred and ninety-five children enrolled; 172 had evaluable ATV pharmacokinetics on day 7.

Intervention: Children were entered in age, dose, and formulation (powder or capsule) cohorts. Intensive pharmacokinetic sampling occurred 7 days after starting ATV. ATV doses were increased or decreased if the 24-h area under the concentration time curves (AUC0-24hr) were less than 30 or more than 90 μg × h/ml, respectively.

Main outcomes: Cohorts satisfied protocol-defined pharmacokinetic criteria if the median ATV AUC0-24hr was 60 μg × h/ml or less, and AUC0-24hr and ATV concentrations 24-h postdose (C24) were more than 30 μg × h/ml and at least 60 ng/ml, respectively, in at least 80% of the children, with no individual AUC0-24hr less than 15 μg × h/ml.

Results: Unboosted ATV capsules satisfied pharmacokinetic criteria at a dose of 520 mg/m for those aged more than 2 to 13 years or less and 620 mg/m for those aged more than 13 to 21 years or less. ATV/r capsules satisfied criteria at a dose of 205 mg/m for those aged more than 2 to 21 years or less. ATV/r powder satisfied criteria at a dose of 310 mg/m for those aged more than 2 to 13 years or less, but pharmacokinetics in those aged 2 years or less were highly variable.

Conclusion: Body surface area-determined doses of ATV capsules and of ATV/r powder and capsules provide ATV exposures in children of more than 2 years that approximate concentrations in adults receiving ATV/r.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Atazanavir Sulfate
  • Child
  • Child, Preschool
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / epidemiology
  • HIV-1 / drug effects*
  • Humans
  • Infant
  • Male
  • Oligopeptides / pharmacokinetics*
  • Oligopeptides / therapeutic use
  • Pyridines / pharmacokinetics*
  • Pyridines / therapeutic use
  • Ritonavir / pharmacokinetics*
  • Ritonavir / therapeutic use
  • South Africa / epidemiology
  • Treatment Outcome
  • United States / epidemiology
  • Young Adult


  • Oligopeptides
  • Pyridines
  • Atazanavir Sulfate
  • Ritonavir