1. Effect of Rifampin-Isoniazid-Containing Antituberculosis Therapy on Efavirenz Pharmacokinetics in HIV-Infected Children 3 to 14 Years Old
- Author
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Hongmei Yang, Anthony Enimil, Sampson Antwi, Charles A. Peloquin, Lubbe Wiesner, Antoinette Ortsin, Michael H. Court, Theresa Opoku, Jennifer Norman, Anima Sarfo, Fizza S. Gillani, Dennis Bosomtwe, David J. Greenblatt, Wael A. Alghamdi, Taimour Y. Langaee, Albert Dompreh, and Awewura Kwara
- Subjects
Cyclopropanes ,Male ,drug-drug interactions ,Antitubercular Agents ,HIV Infections ,chemistry.chemical_compound ,immune system diseases ,Tandem Mass Spectrometry ,antituberculosis therapy ,heterocyclic compounds ,Drug Interactions ,Pharmacology (medical) ,Child ,0303 health sciences ,Coinfection ,Area under the curve ,virus diseases ,efavirenz ,3. Good health ,Infectious Diseases ,tuberculosis ,Anti-Retroviral Agents ,Alkynes ,Child, Preschool ,Reverse Transcriptase Inhibitors ,Female ,Rifampin ,medicine.medical_specialty ,Efavirenz ,Tuberculosis ,Adolescent ,tuberculosis coinfection ,Cmax ,Clinical Therapeutics ,03 medical and health sciences ,Cmin ,children ,Pharmacokinetics ,Internal medicine ,parasitic diseases ,Isoniazid ,medicine ,Humans ,Dosing ,Tuberculosis, Pulmonary ,Pharmacology ,030306 microbiology ,business.industry ,HIV ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,Benzoxazines ,chemistry ,business ,Chromatography, Liquid - 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., 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 Z score, and received a higher median efavirenz weight-adjusted dose. Geometric mean (GM) efavirenz peak concentration (Cmax), concentration at 12 h (C12h), Cmin, and total area under the curve from time 0 to 24 h (AUC0–24h) values were similar in children with HIV infection and those with TB/HIV coinfection during anti-TB therapy. Geometric mean efavirenz C12h, Cmin, and AUC0–24h 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 AUC0–24h 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.)
- Published
- 2019