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Khayelitsha Hospital TB study pharmacokinetic variables: Non compartmental analysis

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posted on 13.08.2019, 10:02 by Charlotte Schutz, Maxwell Chirehwa, David Barr, Amy Ward, Saskia Janssen, Rosie Burton, Robert J. Wilkinson, Muki Shey, Lubbe Wiesner, Paolo Denti, Helen McIlleron, Gary Maartens, Graeme Meintjes
Human immunodeficiency virus associated tuberculosis (HIV-TB) comprise 10% of global tuberculosis cases but contribute a disproportionate 22% of global tuberculosis mortality. HIV-infected patients hospitalized with HIV-TB have high high case fatality rates despite treatment and often present with a clinical picture compatible with sepsis. There is paucity of data in critically ill HIV-infected patients admitted to hospital at the time of tuberculosis diagnosis. Improved, evidence-based treatment interventions in this patient group are urgently needed to improve survival.
We performed intensive pharmacokinetic studies (from 0-8 hours) in a high burden setting (Khayelitsha Hospital, Cape Town), within the routine service. We assessed rifampicin, isoniazid and pyrazinamide exposure in a group of hospitalized HIV-TB patients and a group of outpatients on the third day of standard antituberculosis therapy using non-compartmental analysis. We followed hospitalized patients for 12 weeks to asses survival. We compared pharmacokinetic exposures in hospitalized patients and outpatients; hospitalized patients who survived twelve weeks and those who died; and hospitalized patients presenting with high lactate (more than 2.2 mmol/L) and patient presenting with normal lactate.

Funding

CS was funded by the South African Medical Research Council under the National Health Scholars Programme. GrM, MS and DAB were supported by the Wellcome Trust (098316, 203135, 211360/Z/18/Z and 105165/Z/14/A), GrM was supported by the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation (NRF) of South Africa (Grant No 64787), NRF incentive funding (UID: 85858) and the South African Medical Research Council through its TB and HIV Collaborating Centres Programme with funds received from the National Department of Health (RFA# SAMRC-RFA-CC: TB/HIV/AIDS-01-2014). GaM was supported in part by the NRF (Grant Number 119078). RJW is supported by the Francis Crick Institute, which receives funding from Wellcome (FC00110218), Cancer Research UK (FC00110218), the UK Medical Research Council (FC00110218). RJW also receives support from Wellcome (104803, 203135) and the National Institutes of Health (U01AI115940) and EDCTP (SRIA 2015-1065). PD received NRF incentive funding UID 109056. The funders had no role in the study design, data collection, data analysis, data interpretation, or writing of this report. The opinions, findings and conclusions expressed in this manuscript reflect those of the authors alone.

History

Department/Unit

Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine and Department of Medicine, University of Cape Town, Cape Town, South Africa

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