Suboptimal exposure to anti-TB drugs in a TBM/HIV+ population is not related to anti-retroviral therapy
| Autor: | Steve A. Ward, William W. Hope, David Waterhouse, T T H Chau, Jj J. Farrar, N. T. H. Mai, Nguyen Hoan Phu, Ghaith Aljayyoussi, Tran Tinh Hien, M E Török |
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| Přispěvatelé: | Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Tuberculosis 030106 microbiology Population Antitubercular Agents wc_503 qv_38 Tuberculous meningitis 03 medical and health sciences 0302 clinical medicine Double-Blind Method Internal medicine Antiretroviral Therapy Highly Active HIV Seropositivity medicine Humans Pharmacology (medical) Drug Interactions 030212 general & internal medicine Dosing Treatment Failure education Ethambutol Aged Pharmacology education.field_of_study business.industry Coinfection Pyrazinamide Middle Aged medicine.disease Survival Analysis 3. Good health Tuberculosis Meningeal Immunology qv_268 Female Neurotoxicity Syndromes wf_200 business Rifampicin medicine.drug |
| Zdroj: | CLINICAL PHARMACOLOGY & THERAPEUTICS |
| ISSN: | 0009-9236 1532-6535 |
| Popis: | A placebo-controlled trial that compares the outcomes of immediate vs. deferred initiation of antiretroviral therapy in HIV +ve tuberculous meningitis (TBM) patients was conducted in Vietnam in 2011. Here, the pharmacokinetics of rifampicin, isoniazid, pyrazinamide, and ethambutol were investigated in the presence and absence of anti-HIV treatment in 85 patients. Pharmacokinetic analyses show that HIV therapy has no significant impact on the pharmacokinetics of TB drugs in this cohort. The same population, however, displayed generally low cerebrospinal fluid (CSF) and systemic exposures to rifampicin compared to previously reported HIV -ve cohorts. Elevated CSF concentrations of pyrazinamide, on the other hand, were strongly and independently correlated with increased mortality and neurological toxicity. The findings suggest that the current standard dosing regimens may put the patient at risk of treatment failure from suboptimal rifampicin exposure, and potentially increasing the risk of adverse central nervous system events that are independently correlated with pyrazinamide CSF exposure. |
| Databáze: | OpenAIRE |
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