title: Anti-TB drug concentrations and drug-associated toxicities among TB/HIV-coinfected patients.
abstract: Toxicities due to anti-TB treatment frequently occur among TB/HIV-coinfected patients.
  
  
  
  To determine the association between anti-TB drug concentrations and the occurrence of hepatotoxicity and peripheral neuropathy among TB/HIV-coinfected patients.
  
  
  
  TB/HIV-coinfected patients were started on standard dose anti-TB treatment according to WHO guidelines. Anti-TB drug concentrations were measured 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.
  
  
  
  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 C max 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 C max of rifampicin among those who had hepatotoxicity and those who did not ( P  =   0.322). There was no difference in the isoniazid median C max 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).
  
  
  
  There was no association between rifampicin concentrations and hepatotoxicity or isoniazid concentrations and peripheral neuropathy among TB/HIV-coinfected patients.
authors.affiliation: Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
authors.forename: C
authors.initials: C
authors.lastname: Sekaggya-Wiltshire
authors.affiliation: Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
authors.forename: A
authors.initials: A
authors.lastname: von Braun
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland.|Institute for Medical Virology, University of Zurich, Zurich, Switzerland.
authors.forename: A U
authors.initials: AU
authors.lastname: Scherrer
authors.affiliation: Division of Infectious Disease, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Y C
authors.initials: YC
authors.lastname: Manabe
authors.affiliation: Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
authors.forename: A
authors.initials: A
authors.lastname: Buzibye
authors.affiliation: Department of Clinical Chemistry, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Muller
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Ledergerber
authors.affiliation: Department of Clinical Chemistry, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: U
authors.initials: U
authors.lastname: Gutteck
authors.affiliation: Division of Clinical Pharmacology and Toxicology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Corti
authors.affiliation: Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
authors.forename: A
authors.initials: A
authors.lastname: Kambugu
authors.affiliation: Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.|School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda.
authors.forename: P
authors.initials: P
authors.lastname: Byakika-Kibwika
authors.affiliation: Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
authors.forename: M
authors.initials: M
authors.lastname: Lamorde
authors.affiliation: Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
authors.forename: B
authors.initials: B
authors.lastname: Castelnuovo
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Fehr
authors.affiliation: School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda.
authors.forename: M R
authors.initials: MR
authors.lastname: Kamya
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000009:adverse effects* / Q000097:blood* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology; D060085:Coinfection / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology* / Q000821:virology*; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000453:epidemiology; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000453:epidemiology / Q000209:etiology; D011446:Prospective Studies; D012044:Regression Analysis; D012293:Rifampin / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid; D012293:Rifampin