Observational studyBritish journal of clinical pharmacology2017
Isoniazid clearance is impaired among human immunodeficiency virus/tuberculosis patients with high levels of immune activation.
Observational study in British journal of clinical pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Diagnostic Accuracy of Therapeutic Drug Monitoring During Tuberculosis Treatment.Journal of clinical pharmacology · 2022Article
- Population Pharmacokinetics and Bayesian Dose Adjustment to Advance TDM of Anti-TB Drugs.Clinical pharmacokinetics · 2021Review
- Redox Imbalance and Oxidative DNA Damage During Isoniazid Treatment of HIV-Associated Tuberculosis: A Clinical and Translational Pharmacokinetic Study.Frontiers in pharmacology · 2020Article
- Optimizing ethambutol dosing among HIV/tuberculosis co-infected patients: a population pharmacokinetic modelling and simulation study.The Journal of antimicrobial chemotherapy · 2019Article
- Treatment Complexities Among Patients with Tuberculosis in a High HIV Prevalence Cohort in the United States.AIDS research and human retroviruses · 2018Article
- Pharmacokinetics of tuberculosis drugs in HIV-infected patients from Irkutsk, Russian Federation: redefining drug activity.The European respiratory journal · 2018Article
- Levofloxacin Population Pharmacokinetics in South African Children Treated for Multidrug-Resistant Tuberculosis.Antimicrobial agents and chemotherapy · 2018Observational
- Markers of gut dysfunction do not explain low rifampicin bioavailability in HIV-associated TB.The Journal of antimicrobial chemotherapy · 2017Article
- Isoniazid clearance is impaired among human immunodeficiency virus/tuberculosis patients with high levels of immune activation.British journal of clinical pharmacology · 2017Observational
- Pyrazinamide clearance is impaired among HIV/tuberculosis patients with high levels of systemic immune activation.PloS one · 2017Article
- Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
aimsImmune activation, which is characteristic of both tuberculosis (TB) and human immunodeficiency virus (HIV) infection, is associated with impaired drug metabolism. We tested the hypothesis that elevated levels of systemic immune activation among adults with HIV/TB initiating antiretroviral therapy (ART) would be associated with impaired clearance of isoniazid.
methodsWe conducted a prospective observational study of isoniazid pharmacokinetics (PK) and systemic immune activation prior to and 1 month after ART initiation. Nonlinear mixed effects analysis was performed to measure the covariate effect of immune activation on isoniazid clearance in a model that also included N-acetyltransferase-2 (NAT-2) genotype and interoccasional variability on clearance (thereby analyzing the PK data before and after ART initiation in a single model).
resultsWe enrolled 40 patients in the PK visit prior to ART, and 24 patients returned for the second visit a median of 33 days after initiating antiretroviral therapy. The isoniazid concentration data were best described by a two-compartment model with first-order elimination. After accounting for NAT-2 genotype, increasing levels of CD38 and HLA-DR expression on CD8+ T cells (CD38
conclusionHIV/TB patients with high levels of immune activation demonstrated impaired isoniazid clearance. Future efforts should determine the role of this relationship in clinical hepatotoxicity events.
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