In:
Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 63, No. 1 ( 2019-01)
Kurzfassung:
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 ( C max ), concentration at 12 h ( C 12h ), C min , and total area under the curve from time 0 to 24 h (AUC 0–24h ) values were similar in children with HIV infection and those with TB/HIV coinfection during anti-TB therapy. Geometric mean efavirenz C 12h , C min , and AUC 0–24h 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 AUC 0–24h 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.)
Materialart:
Online-Ressource
ISSN:
0066-4804
,
1098-6596
DOI:
10.1128/AAC.01657-18
Sprache:
Englisch
Verlag:
American Society for Microbiology
Publikationsdatum:
2019
ZDB Id:
1496156-8
SSG:
12
SSG:
15,3
