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

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.

© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Figures

Figure 1

Association between rifampicin concentrations and grade of hepatotoxicity. Box plot showing rifampicin concentrations for each category of hepatotoxicity: the top of each box represents the 75th percentile (Q3), the bottom the 25th percentile (Q1), the horizontal line within each box represents the 50th percentile (median) rifampicin concentrations. The top whisker represents Q3 + (1.5×IQR) while the bottom represents Q1 – (1.5×IQR). The dots represent outliers.

Figure 2

Association between isoniazid concentrations and presence of peripheral neuropathy. Box plot showing isoniazid concentrations for patients with and without peripheral neuropathy. Boxplot conventions are the same as in Figure 1.