Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2017 Apr 1;72(4):1172-1177.
doi: 10.1093/jac/dkw534.

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

C Sekaggya-Wiltshire  1 , A von Braun  1 , A U Scherrer  2   3 , Y C Manabe  4 , A Buzibye  1 , D Muller  5 , B Ledergerber  2 , U Gutteck  5 , N Corti  6 , A Kambugu  1 , P Byakika-Kibwika  1   7 , M Lamorde  1 , B Castelnuovo  1 , J Fehr  2 , M R Kamya  7
Affiliations
Observational Study

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

C Sekaggya-Wiltshire et al. J Antimicrob Chemother. .

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.

PubMed Disclaimer

Figures

Figure 1
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
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.
See this image and copyright information in PMC

References

    1. WHO. Global Tuberculosis Report 2016 http://www.who.int/tb/publications/global_report/en/.
    1. Arbex MA, Varella Mde C, Siqueira HR. et al. Antituberculosis drugs: drug interactions, adverse effects, and use in special situations. Part 1: first-line drugs. J Bras Pneumol 2010; 36: 626–40. - PubMed
    1. Girling DJ. The hepatic toxicity of antituberculosis regimens containing isoniazid, rifampicin and pyrazinamide. Tubercle 1978; 59: 13–32. - PubMed
    1. Dworkin MS, Adams MR, Cohn DL. et al. Factors that complicate the treatment of tuberculosis in HIV-infected patients. J Acquir Immune Defic Syndr 2005; 39: 464–70. - PubMed
    1. Ruslami R, Nijland HM, Alisjahbana B. et al. Pharmacokinetics and tolerability of a higher rifampin dose versus the standard dose in pulmonary tuberculosis patients. Antimicrob Agents Chemother 2007; 51: 2546–51. - PMC - PubMed

Publication types

MeSH terms