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Suboptimal Exposure to Anti-TB Drugs in a TBM/HIV+ Population is not Related to Anti-retroviral Therapy.

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Török, M E, Aljayyoussi, Ghaith, Waterhouse, David, Chau, Tth, Mai, Nth, Phu, N H, Hien, T T, Hope, W, Farrar, J J and Ward, Steve ORCID: https://orcid.org/0000-0003-2331-3192 (2017) 'Suboptimal Exposure to Anti-TB Drugs in a TBM/HIV+ Population is not Related to Anti-retroviral Therapy.'. Clinical pharmacology and therapeutics, Vol 103, Issue 3, pp. 449-457.

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Abstract

A placebo-controlled trial that compares the outcomes of immediate versus 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 upon the pharmacokinetics of TB drugs in this cohort. The same population, however, displayed generally low 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 CNS events which are independently correlated with pyrazinamide CSF exposure.

Item Type: Article
Subjects: QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 268 Antitubercular agents. Antitubercular antibiotics
QV Pharmacology > QV 38 Drug action.
WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503 Acquired immunodeficiency syndrome. HIV infections
WF Respiratory System > Tuberculosis > WF 200 Tuberculosis (General)
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI): https://doi.org/10.1002/cpt.646
SWORD Depositor: JISC Pubrouter
Depositing User: Stacy Murtagh
Date Deposited: 09 May 2017 15:09
Last Modified: 13 Feb 2018 09:40
URI: http://archive.lstmed.ac.uk/id/eprint/6852

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