Anti-TB drug concentrations and drug-associated toxicities among TB/HIV-coinfected patients

C. Sekaggya-Wiltshire, A. von Braun, A. U. Scherrer, Y. C. Manabe, A. Buzibye, D. Muller, B. Ledergerber, U. Gutteck, N. Corti, A. Kambugu, P. Byakika-Kibwika, M. Lamorde, B. Castelnuovo, J. Fehr, M. R. Kamya

Research output: Research - peer-reviewArticle

Abstract

Background: Toxicities due to anti-TB treatment frequently occur among TB/HIV-coinfected patients. Objectives: To determine the association between anti-TB drug concentrations and the occurrence of hepatotoxicity and peripheral neuropathy among TB/HIV-coinfected patients. Methods: TB/HIV-coinfected patients were started on standard dose anti-TB treatment according toWHO guidelines. Anti-TB drug concentrations weremeasured using HPLC 1, 2 and 4 h after drug intake at 2, 8 and 24 weeks following initiation of TB treatment. Participants were assessed for hepatotoxicity using Division of AIDS toxicity tables and for peripheral neuropathy using clinical assessment of tendon reflexes, vibration sensation or symptoms. Cox regression was used to determine the association between toxicities and drug concentrations. Results: Of the 268 patients enrolled, 58% were male with a median age of 34 years. Participants with no hepatotoxicity or mild, moderate and severe hepatotoxicity had a median Cmax of 6.57 (IQR 4.83-9.41) μg/mL, 7.39 (IQR 5.10-10.20) μg/mL, 7.00 (IQR 6.05-10.95) μg/mL and 3.86 (IQR 2.81-14.24) μg/mL, respectively. There was no difference in the median Cmax of rifampicin among those who had hepatotoxicity and those who did not (P"0.322). There was no difference in the isoniazid median Cmax among those who had peripheral neuropathy 2.34 (1.52-3.23) μg/mL and those who did not 2.21 (1.45-3.11) μg/mL (P"0.49). Conclusions: There was no association between rifampicin concentrations and hepatotoxicity or isoniazid concentrations and peripheral neuropathy among TB/HIV-coinfected patients.

LanguageEnglish (US)
Pages1172-1177
Number of pages6
JournalJournal of Antimicrobial Chemotherapy
Volume72
Issue number4
DOIs
StatePublished - 2017

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Drug-Related Side Effects and Adverse Reactions
HIV
Pharmaceutical Preparations
Peripheral Nervous System Diseases
Therapeutics
Isoniazid
Rifampin
Stretch Reflex
Vibration
Acquired Immunodeficiency Syndrome
High Pressure Liquid Chromatography
Guidelines

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Sekaggya-Wiltshire, C., von Braun, A., Scherrer, A. U., Manabe, Y. C., Buzibye, A., Muller, D., ... Kamya, M. R. (2017). Anti-TB drug concentrations and drug-associated toxicities among TB/HIV-coinfected patients. Journal of Antimicrobial Chemotherapy, 72(4), 1172-1177. DOI: 10.1093/jac/dkw534

Anti-TB drug concentrations and drug-associated toxicities among TB/HIV-coinfected patients. / Sekaggya-Wiltshire, C.; von Braun, A.; Scherrer, A. U.; Manabe, Y. C.; Buzibye, A.; Muller, D.; Ledergerber, B.; Gutteck, U.; Corti, N.; Kambugu, A.; Byakika-Kibwika, P.; Lamorde, M.; Castelnuovo, B.; Fehr, J.; Kamya, M. R.

In: Journal of Antimicrobial Chemotherapy, Vol. 72, No. 4, 2017, p. 1172-1177.

Research output: Research - peer-reviewArticle

Sekaggya-Wiltshire, C, von Braun, A, Scherrer, AU, Manabe, YC, Buzibye, A, Muller, D, Ledergerber, B, Gutteck, U, Corti, N, Kambugu, A, Byakika-Kibwika, P, Lamorde, M, Castelnuovo, B, Fehr, J & Kamya, MR 2017, 'Anti-TB drug concentrations and drug-associated toxicities among TB/HIV-coinfected patients' Journal of Antimicrobial Chemotherapy, vol 72, no. 4, pp. 1172-1177. DOI: 10.1093/jac/dkw534
Sekaggya-Wiltshire C, von Braun A, Scherrer AU, Manabe YC, Buzibye A, Muller D et al. Anti-TB drug concentrations and drug-associated toxicities among TB/HIV-coinfected patients. Journal of Antimicrobial Chemotherapy. 2017;72(4):1172-1177. Available from, DOI: 10.1093/jac/dkw534
Sekaggya-Wiltshire, C. ; von Braun, A. ; Scherrer, A. U. ; Manabe, Y. C. ; Buzibye, A. ; Muller, D. ; Ledergerber, B. ; Gutteck, U. ; Corti, N. ; Kambugu, A. ; Byakika-Kibwika, P. ; Lamorde, M. ; Castelnuovo, B. ; Fehr, J. ; Kamya, M. R./ Anti-TB drug concentrations and drug-associated toxicities among TB/HIV-coinfected patients. In: Journal of Antimicrobial Chemotherapy. 2017 ; Vol. 72, No. 4. pp. 1172-1177
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AU - Sekaggya-Wiltshire,C.

AU - von Braun,A.

AU - Scherrer,A. U.

AU - Manabe,Y. C.

AU - Buzibye,A.

AU - Muller,D.

AU - Ledergerber,B.

AU - Gutteck,U.

AU - Corti,N.

AU - Kambugu,A.

AU - Byakika-Kibwika,P.

AU - Lamorde,M.

AU - Castelnuovo,B.

AU - Fehr,J.

AU - Kamya,M. R.

PY - 2017

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N2 - Background: Toxicities due to anti-TB treatment frequently occur among TB/HIV-coinfected patients. Objectives: To determine the association between anti-TB drug concentrations and the occurrence of hepatotoxicity and peripheral neuropathy among TB/HIV-coinfected patients. Methods: TB/HIV-coinfected patients were started on standard dose anti-TB treatment according toWHO guidelines. Anti-TB drug concentrations weremeasured using HPLC 1, 2 and 4 h after drug intake at 2, 8 and 24 weeks following initiation of TB treatment. Participants were assessed for hepatotoxicity using Division of AIDS toxicity tables and for peripheral neuropathy using clinical assessment of tendon reflexes, vibration sensation or symptoms. Cox regression was used to determine the association between toxicities and drug concentrations. Results: Of the 268 patients enrolled, 58% were male with a median age of 34 years. Participants with no hepatotoxicity or mild, moderate and severe hepatotoxicity had a median Cmax of 6.57 (IQR 4.83-9.41) μg/mL, 7.39 (IQR 5.10-10.20) μg/mL, 7.00 (IQR 6.05-10.95) μg/mL and 3.86 (IQR 2.81-14.24) μg/mL, respectively. There was no difference in the median Cmax of rifampicin among those who had hepatotoxicity and those who did not (P"0.322). There was no difference in the isoniazid median Cmax among those who had peripheral neuropathy 2.34 (1.52-3.23) μg/mL and those who did not 2.21 (1.45-3.11) μg/mL (P"0.49). Conclusions: There was no association between rifampicin concentrations and hepatotoxicity or isoniazid concentrations and peripheral neuropathy among TB/HIV-coinfected patients.

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