Journal article
Effect of Rifampin-Isoniazid-Containing Antituberculosis Therapy on Efavirenz Pharmacokinetics in HIV-Infected Children 3 to 14 Years Old
Antimicrobial agents and chemotherapy, Vol.63(1)
01/2019
Handle:
https://hdl.handle.net/2376/101260
PMCID: PMC6325194
PMID: 30397066
Abstract
We compared efavirenz pharmacokinetic (PK) parameters in children with tuberculosis (TB)/human immunodeficiency virus (HIV) coinfection on and off first-line antituberculosis therapy to that in HIV-infected children. Children 3 to 14 years old with HIV infection, with and without TB, were treated with standard efavirenz-based antiretroviral therapy without any efavirenz dose adjustments. The new World Health Organization-recommended antituberculosis drug dosages were used in the coinfected participants. Steady-state efavirenz concentrations after 4 weeks of antiretroviral therapy were measured using validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) assays. Pharmacokinetic parameters were calculated using noncompartmental analysis. Between groups, PK parameters were compared by Wilcoxon rank-sum test and within group by signed-rank test. Of the 105 participants, 43 (41.0%) had TB coinfection. Children with TB/HIV coinfection compared to those with HIV infection were younger, had lower median weight-for-age
score, and received a higher median efavirenz weight-adjusted dose. Geometric mean (GM) efavirenz peak concentration (
), concentration at 12 h (
),
, and total area under the curve from time 0 to 24 h (AUC
) values were similar in children with HIV infection and those with TB/HIV coinfection during anti-TB therapy. Geometric mean efavirenz
,
, and AUC
values were lower in TB/HIV-coinfected patients off anti-TB therapy than in the children with HIV infection or TB/HIV coinfection on anti-TB therapy. Efavirenz clearance was lower and AUC
was higher on than in patients off anti-TB therapy. Reduced efavirenz clearance by first-line anti-TB therapy at the population level led to similar PK parameters in HIV-infected children with and without TB coinfection. Our findings do not support modification of efavirenz weight-band dosing guidelines based on TB coinfection status in children. (The study was registered with ClinicalTrials.gov under registration number NCT01704144.).
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Details
- Title
- Effect of Rifampin-Isoniazid-Containing Antituberculosis Therapy on Efavirenz Pharmacokinetics in HIV-Infected Children 3 to 14 Years Old
- Creators
- Awewura Kwara - College of Medicine and Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA awewura.kwara@medicine.ufl.eduHongmei Yang - Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USASampson Antwi - Department of Child Health, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, GhanaAnthony Enimil - Department of Child Health, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, GhanaFizza S Gillani - Deaprtment of Medicine, The Miriam Hospital, Providence, Rhode Island, USAAlbert Dompreh - Directorate of Child Health, Komfo Anokye Teaching Hospital, Kumasi, GhanaAntoinette Ortsin - Directorate of Child Health, Komfo Anokye Teaching Hospital, Kumasi, GhanaTheresa Opoku - Directorate of Child Health, Komfo Anokye Teaching Hospital, Kumasi, GhanaDennis Bosomtwe - Directorate of Child Health, Komfo Anokye Teaching Hospital, Kumasi, GhanaAnima Sarfo - Directorate of Child Health, Komfo Anokye Teaching Hospital, Kumasi, GhanaLubbe Wiesner - Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South AfricaJennifer Norman - Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South AfricaWael A Alghamdi - Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha, Saudi ArabiaTaimour Langaee - Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, Florida, USACharles A Peloquin - Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, Florida, USAMichael H Court - Program in Individualized Medicine, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USADavid J Greenblatt - Graduate Program in Pharmacology and Experimental Therapeutics, Sackler School of Graduate Biomedical Sciences and Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, Massachusetts, USA
- Publication Details
- Antimicrobial agents and chemotherapy, Vol.63(1)
- Academic Unit
- Veterinary Clinical Sciences, Department of
- Publisher
- United States
- Grant note
- R01 HD071779 / NICHD NIH HHS UM1 AI106701 / NIAID NIH HHS P30 AI042853 / NIAID NIH HHS UM1 AI068636 / NIAID NIH HHS U01 AI068632 / NIAID NIH HHS P30 AI078498 / NIAID NIH HHS UM1 AI068632 / NIAID NIH HHS UM1 AI068634 / NIAID NIH HHS R01 GM102130 / NIGMS NIH HHS
- Identifiers
- 99900546633701842
- Language
- English
- Resource Type
- Journal article