Original Research

Rechallenge after anti-tuberculosis drug-induced liver injury in a high HIV prevalence cohort

Muhammed Shiraz Moosa, Gary Maartens, Hannah Gunter, Shaazia Allie, Mohamed F. Chughlay, Mashiko Setshedi, Sean Wasserman, David F. Stead, Karen Cohen
Southern African Journal of HIV Medicine | Vol 23, No 1 | a1376 | DOI: https://doi.org/10.4102/sajhivmed.v23i1.1376 | © 2022 Muhammed Shiraz Moosa, Gary Maartens, Hannah Gunter, Shaazia Allie, Mohamed F. Chughlay, Mashiko Setshedi, Sean Wasserman, David F. Stead, Karen Cohen | This work is licensed under CC Attribution 4.0
Submitted: 01 February 2022 | Published: 14 June 2022

About the author(s)

Muhammed Shiraz Moosa, Department of Medicine, New Somerset Hospital, Cape Town, South Africa; and, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
Gary Maartens, Department of Medicine, Division of Clinical Pharmacology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
Hannah Gunter, Department of Medicine, Division of Clinical Pharmacology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
Shaazia Allie, Department of Medicine, Division of Clinical Pharmacology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
Mohamed F. Chughlay, Department of Medicine, Division of Clinical Pharmacology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
Mashiko Setshedi, Department of Medicine, Division of Gastroenterology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
Sean Wasserman, Department of Medicine, Division of Infectious Diseases, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
David F. Stead, Department of Medicine, New Somerset Hospital, Cape Town, South Africa; and, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
Karen Cohen, Department of Medicine, Division of Clinical Pharmacology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa


Share this article

Bookmark and Share

Abstract

Background: There are limited data on the outcomes of rechallenge with anti-tuberculosis therapy (ATT) following anti-tuberculosis drug-induced liver injury (AT-DILI) in a high HIV prevalence setting.

Objectives: To describe the outcomes of rechallenge with first-line ATT.

Method: Hospitalised participants with AT-DILI who were enrolled into a randomised controlled trial of N-acetylcysteine in Cape Town, South Africa, were followed up until completion of ATT rechallenge. We described rechallenge outcomes, and identified associations with recurrence of liver injury on rechallenge (positive rechallenge).

Results: Seventy-nine participants were rechallenged of whom 41 (52%) were female. Mean age was 37 years (standard deviation [s.d.] ±10). Sixty-eight (86%) were HIV-positive, of whom 34 (50%) were on antiretroviral therapy (ART) at time of AT-DILI presentation. Five participants had serious adverse reactions to an aminoglycoside included in the alternate ATT regimen given after first-line ATT interruption: acute kidney injury in three and hearing loss in two. The median time from first-line ATT interruption to start of first-line ATT rechallenge was 13 days (interquartile range [IQR]: 8–18 days). Antiretroviral therapy was interrupted for a median of 32 days (IQR: 17–58) among HIV-positive participants on ART before AT-DILI. Fourteen participants had positive rechallenge (18%). Positive rechallenge was associated with pyrazinamide rechallenge (P = 0.005), female sex (P = 0.039) and first episode of tuberculosis (TB) (P = 0.032).

Conclusion: Rechallenge was successful in most of our cohort. Pyrazinamide rechallenge should be carefully considered.


Keywords

tuberculosis; anti-tuberculosis drugs; drug-induced liver injury; positive rechallenge; pyrazinamide; treatment interruption

Metrics

Total abstract views: 286
Total article views: 99


Crossref Citations

No related citations found.