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Pharmacokinetics of anti-tuberculosis drugs in HIV-positive and HIV-negative adults in Malawi

Pharmacokinetics of anti-tuberculosis drugs in HIV-positive and HIV-negative adults in Malawi. J.J. van Oosterhout 1,2 , F. Dzinjalamala 3 , A. Dimba 4 , D. Waterhouse 5 , G. Davies 6,7 , M. Molyneux 5,6 , E. Molyneux 8 , S. Ward 7

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Pharmacokinetics of anti-tuberculosis drugs in HIV-positive and HIV-negative adults in Malawi

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  1. Pharmacokinetics of anti-tuberculosis drugs in HIV-positive and HIV-negative adults in Malawi J.J. van Oosterhout 1,2, F. Dzinjalamala3, A. Dimba 4, D. Waterhouse 5, G. Davies 6,7, M. Molyneux5,6, E. Molyneux8, S. Ward7 1College of Medicine, Department of Medicine, Blantyre, Malawi, 2Dignitas International, Zomba, Malawi, 3 College of Medicine, Department of Biochemistry, Blantyre, Malawi, 4National Tuberculosis Control Program, Lilongwe, Malawi, 5Liverpool School of Tropical Medicine, Liverpool, United Kingdom, 6Malawi-Liverpool-Wellcome Trust Clinical Research Programme Unit, Blantyre, Malawi, 7University of Liverpool, Liverpool, United Kingdom, 8College of Medicine, Department of Pediatrics, Blantyre, Malawi

  2. Background • High HIV prevalence and high TB-HIV co-infection rate in Malawi • High prevalence of malnutrition • Few pharmacokinetic studies of TB drugs sub-Saharan Africa • Some data suggest HIV infection affects TB drug levels Aims • Pharmacokinetic profiles of 4 drugs of Malawi first line TB treatment regimen (RHZE) • Impact of HIV status and other factors on TB drug pharmacokinetics

  3. Methods • Intensive PK study adult Malawians • Sputum AFB smear positive PTB • Intensive phase TB treatment • Exclusion: vomiting, diarrhea; Hb <8.0 g/dL; recent stop ART • FDC formulations; dosing according to recommended weight bands • Sampling: 0 – 0.5 – 1 – 2 – 3 – 4 – 6 – 8 – 24 • R and Z: high-performance liquid chromatography • H and E: mass spectrometry

  4. Patient characteristics • N=47 • 51% male • Mean age 34 • 30 (65%) HIV+ • Median CD4 = 167 (53% <200) cells/µL • 14 (47%) on ART • Median weight 54.5 kg • Median BMI 19.2 (46% <18.5)

  5. Results compatible with other studies from the region A. Tostmann et al; AAC 2013. B. McIlleron et al; AAC 2006. C. Saleri et al; JAC 2012

  6. No significant impact on main PKparameters: • Dose, weight, weight-adjusted dose, gender, age • HIV infection, being on ART

  7. Potential causes of low rifampicin exposure • Dose–weight • Malnutrition • HIV infection • Severe illness • Sample collection/transport • Breakfast • Pharmaco-genetic factors • SLCO1B1 polymorphisms • Quality of drug formulation

  8. Conclusions: - PKresults comparable to SSA studies low rifampicin exposure - No impact of HIV infection Acknowledgements: National TB Control Programme; University of Liverpool

  9. 8-24 3-5 20-50 2-6

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