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
Clinical Trial
. 2015 Sep;19(9):1039-44, i-v.
doi: 10.5588/ijtld.14.0829.

Three months of weekly rifapentine plus isoniazid is less hepatotoxic than nine months of daily isoniazid for LTBI

E E Bliven-Sizemore  1 , T R Sterling  2 , N Shang  1 , D Benator  3 , K Schwartzman  4 , R Reves  5 , J Drobeniuc  6 , N Bock  1 , M E Villarino  1 ; TB Trials Consortium
Collaborators, Affiliations
Clinical Trial

Three months of weekly rifapentine plus isoniazid is less hepatotoxic than nine months of daily isoniazid for LTBI

E E Bliven-Sizemore et al. Int J Tuberc Lung Dis. 2015 Sep.

Abstract

Setting: Nine months of daily isoniazid (9H) and 3 months of once-weekly rifapentine plus isoniazid (3HP) are recommended treatments for latent tuberculous infection (LTBI). The risk profile for 3HP and the contribution of hepatitis C virus (HCV) infection to hepatotoxicity are unclear.

Objectives: To evaluate the hepatotoxicity risk associated with 3HP compared to 9H, and factors associated with hepatotoxicity.

Design: Hepatotoxicity was defined as aspartate aminotransferase (AST) >3 times the upper limit of normal (ULN) with symptoms (nausea, vomiting, jaundice, or fatigue), or AST >5 x ULN. We analyzed risk factors among adults who took at least 1 dose of their assigned treatment. A nested case-control study assessed the role of HCV.

Results: Of 6862 participants, 77 (1.1%) developed hepatotoxicity; 52 (0.8%) were symptomatic; 1.8% (61/3317) were on 9H and 0.4% (15/3545) were on 3HP (P < 0.0001). Risk factors for hepatotoxicity were age, female sex, white race, non-Hispanic ethnicity, decreased body mass index, elevated baseline AST, and 9H. In the case-control study, HCV infection was associated with hepatotoxicity when controlling for other factors.

Conclusion: The risk of hepatotoxicity during LTBI treatment with 3HP was lower than the risk with 9H. HCV and elevated baseline AST were risk factors for hepatotoxicity. For persons with these risk factors, 3HP may be preferred.

PubMed Disclaimer

Conflict of interest statement

Potential conflicts of interest and financial disclosure: TRS: Sanofi consultation for data presented to the Food and Drug Administration (Washington DC, USA). Otsuka (Tokyo, Japan): member of data safety monitoring board for tuberculosis clinical trial. All other authors report no conflicts of interest apart from those already disclosed above.

Comment in

References

    1. Dye C, Scheele S, Dolin P, Pathania V, Raviglione MC. Global burden of tuberculosis. Estimated incidence, prevalence, and mortality by country. JAMA. 1999;282:677–686. - PubMed
    1. American Thoracic Society, Centers for Disease Control and Prevention. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med. 2000;161(4 Pt 2):S221–S247. - PubMed
    1. Institute of Medicine. Ending neglect: the elimination of tuberculosis in the United States. Washington DC, USA: National Academy of Sciences; 2000.
    1. World Health Organization. Guidelines for intensified tuberculosis case-finding and isoniazid preventive therapy for people living with HIV in resource-constrained settings. Geneva, Switzerland: WHO; 2011. [Accessed June 2015]. http://whqlibdoc.who.int/publications/2011/9789241500708_eng.pdf.
    1. Sterling TR, Bethel J, Goldberg S, Weinfurter P, Yun L, Horsburgh CR. The scope and impact of treatment of latent tuberculosis infection in the United States and Canada. Am J Respir Crit Care Med. 2006;173:927–931. - PubMed

Publication types

MeSH terms