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

J Antimicrob Chemother. 2017 Apr 1;72(4):1172-1177. doi: 10.1093/jac/dkw534.

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 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.

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 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).

Conclusions: There was no association between rifampicin concentrations and hepatotoxicity or isoniazid concentrations and peripheral neuropathy among TB/HIV-coinfected patients.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Antitubercular Agents / adverse effects*
  • Antitubercular Agents / blood*
  • Antitubercular Agents / therapeutic use
  • Chemical and Drug Induced Liver Injury / epidemiology
  • Chemical and Drug Induced Liver Injury / etiology
  • Coinfection / drug therapy
  • Coinfection / epidemiology
  • Coinfection / microbiology*
  • Coinfection / virology*
  • Female
  • HIV Infections / complications
  • HIV Infections / epidemiology
  • Humans
  • Isoniazid / administration & dosage
  • Isoniazid / adverse effects
  • Isoniazid / therapeutic use
  • Male
  • Middle Aged
  • Peripheral Nervous System Diseases / epidemiology
  • Peripheral Nervous System Diseases / etiology
  • Prospective Studies
  • Regression Analysis
  • Rifampin / adverse effects
  • Rifampin / blood
  • Rifampin / therapeutic use
  • Tuberculosis / complications
  • Tuberculosis / drug therapy*
  • Tuberculosis / epidemiology
  • Tuberculosis / microbiology
  • Tuberculosis, Pulmonary / drug therapy
  • Young Adult

Substances

  • Antitubercular Agents
  • Isoniazid
  • Rifampin