Early antituberculosis drug exposure in hospitalized patients with human immunodeficiency virus-associated tuberculosis

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Schutz, Charlotte, Chirehwa, Maxwell, Barr, David ORCID: 0000-0002-2922-9381, Ward, Amy, Janssen, Saskia, Burton, Rosie, Wilkinson, Robert J, Shey, Muki, Wiesner, Lubbe, Denti, Paolo et al (show 3 more authors) , McIlleron, Helen, Maartens, Gary and Meintjes, Graeme (2020) Early antituberculosis drug exposure in hospitalized patients with human immunodeficiency virus-associated tuberculosis. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 86 (5). pp. 966-978.

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Abstract

<h4>Aims</h4>Patients hospitalized at the time of human immunodeficiency virus-associated tuberculosis (HIV-TB) diagnosis have high early mortality. We hypothesized that compared to outpatients, there would be lower anti-TB drug exposure in hospitalized HIV-TB patients, and amongst hospitalized patients exposure would be lower in patients who die or have high lactate (a sepsis marker).<h4>Methods</h4>We performed pharmacokinetic sampling in hospitalized HIV-TB patients and outpatients. Plasma rifampicin, isoniazid and pyrazinamide concentrations were measured in samples collected predose and at 1, 2.5, 4, 6 and 8 hours on the third day of standard anti-TB therapy. Twelve-week mortality was ascertained for inpatients. Noncompartmental pharmacokinetic analysis was performed.<h4>Results</h4>Pharmacokinetic data were collected in 59 hospitalized HIV-TB patients and 48 outpatients. Inpatient 12-week mortality was 11/59 (19%). Rifampicin, isoniazid and pyrazinamide exposure was similar between hospitalized and outpatients (maximum concentration [C_max ]: 7.4 vs 8.3 μg mL^-1 , P = .223; 3.6 vs 3.5 μg mL^-1 , P = .569; 50.1 vs 46.8 μg mL^-1 , P = .081; area under the concentration-time curve from 0 to 8 hours: 41.0 vs 43.8 mg h L^-1 , P = 0.290; 13.5 vs 12.4 mg h L^-1 , P = .630; 316.5 vs 292.2 mg h L^-1 , P = .164, respectively) and not lower in inpatients who died. Rifampicin and isoniazid C_max were below recommended ranges in 61% and 39% of inpatients and 44% and 35% of outpatients. Rifampicin exposure was higher in patients with lactate >2.2 mmol L^-1 .<h4>Conclusion</h4>Mortality in hospitalized HIV-TB patients was high. Early anti-TB drug exposure was similar to outpatients and not lower in inpatients who died. Rifampicin and isoniazid C_max were suboptimal in 61% and 39% of inpatients and rifampicin exposure was higher in patients with high lactate. Treatment strategies need to be optimized to improve survival.

Item Type:	Article
Uncontrolled Keywords:	human immunodeficiency virus, tuberculosis, treatment, pharmacokinetics
Depositing User:	Symplectic Admin
Date Deposited:	20 Jan 2020 16:30
Last Modified:	19 Jan 2023 00:08
DOI:	10.1111/bcp.14207
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3071395