title: Steady-state pharmacokinetics of tenofovir-based regimens in HIV-infected pediatric patients.
abstract: HIV-infected children are treated with tenofovir in combination with other, potentially interacting, antiretroviral agents. We report the pharmacokinetic parameters of tenofovir in combination with efavirenz, darunavir-ritonavir, or atazanavir-ritonavir in HIV-infected children. HIV-infected patients 8 to 18 years of age receiving a tenofovir (300 mg)-based regimen containing efavirenz (300 or 600 mg) once daily (group 1), darunavir (300 or 600 mg)-ritonavir (100 mg) twice daily (group 2), or atazanavir (150 to 400 mg)-ritonavir (100 mg) once daily (group 3) were enrolled. Plasma samples were collected over a 24-h time interval. The 90% confidence intervals (90% CI) of the geometric means for the area under the plasma concentration-time curve (AUC) and the minimum concentration of drug in serum (C(min)) of each antiretroviral were computed and checked for overlap with intervals bracketing published values obtained in adult or pediatric studies demonstrating safety and/or efficacy. Group 1 efavirenz plasma concentrations were observed to be higher in patients receiving fixed-dose combination tablets compared with subjects receiving the individual formulation. In group 2, tenofovir and darunavir exposure was observed to be lower than expected. In group 3, tenofovir and atazanavir administered concomitantly produced exposures similar to those published for adult patients. The 90% CI of AUC and C(min) for tenofovir overlapped the target range for all combinations. Informal comparisons of treatment groups did not indicate any advantage to any combination with respect to tenofovir exposure. Further study of exposures achieved with antiretrovirals administered in combination is warranted.
authors.affiliation: University of Alabama at Birmingham, Division of Clinical Pharmacology, 1530 3rd Avenue South, Shelby 1170, Birmingham, AL 35294-0019, USA. jennifer.king@ccc.uab.edu
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: King
authors.forename: Ram
authors.initials: R
authors.lastname: Yogev
authors.forename: Patrick
authors.initials: P
authors.lastname: Jean-Philippe
authors.forename: Bobbie
authors.initials: B
authors.lastname: Graham
authors.forename: Andrew
authors.initials: A
authors.lastname: Wiznia
authors.forename: Paula
authors.initials: P
authors.lastname: Britto
authors.forename: Vincent
authors.initials: V
authors.lastname: Carey
authors.forename: Rohan
authors.initials: R
authors.lastname: Hazra
authors.forename: Edward P
authors.initials: EP
authors.lastname: Acosta
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000069446:Atazanavir Sulfate; D048588:Benzoxazines / Q000008:administration & dosage / Q000627:therapeutic use; D002648:Child; D003521:Cyclopropanes; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000627:therapeutic use; D063065:Organophosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use; D000068698:Tenofovir
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D000069446:Atazanavir Sulfate; D000068698:Tenofovir; D000225:Adenine; C098320:efavirenz; D019438:Ritonavir