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Adverse events with isoniazid preventive therapy: experience from a large trial
Alison D Grant1, Kathryn T Mngadi, Clare L van Halsema
1Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK. alison.grant@lshtm.ac.uk
AIDS (London, England)
|November 17, 2010
Summary
Isoniazid preventive therapy (IPT) showed a very low risk of adverse events, including hepatotoxicity, in South African gold miners. Clinical screening and monitoring are effective for safe IPT administration.
Area of Science:
- Public Health
- Infectious Diseases
- Pharmacovigilance
Background:
- Isoniazid preventive therapy (IPT) is crucial for tuberculosis (TB) control, especially in high-prevalence populations.
- Gold miners in South Africa face a significant TB burden with high HIV co-infection rates.
- Understanding isoniazid-related adverse events is vital for safe implementation of community-wide IPT.
Purpose of the Study:
- To assess the incidence and types of isoniazid-related adverse events in a large cohort of South African gold miners.
- To evaluate the safety and efficacy of clinical criteria for screening and monitoring during IPT.
- To identify risk factors associated with isoniazid toxicity in this specific occupational group.
Main Methods:
- A cluster-randomized study involving community-wide IPT among gold miners.
- Pre-IPT screening for active TB and isoniazid toxicity risk using questionnaires and chest radiographs.
- Systematic monitoring for study-defined adverse events, with liver function tests performed only when clinically indicated.
- A substudy to assess minor IPT-related adverse events through participant questioning at specified intervals.
Main Results:
- Out of 24,221 participants, 130 (0.54%) experienced study-defined adverse events, including hypersensitivity rash (0.25%) and peripheral neuropathy (0.21%).
- Clinical hepatotoxicity occurred in 0.07% of participants and was associated with alcohol consumption (OR 3.9).
- Serious adverse events included two cases of hepatotoxicity (one fatal) and two convulsions; 65.1% of participants in a substudy reported improved health and appetite on IPT.
Conclusions:
- The overall risk of adverse events, particularly hepatotoxicity, associated with IPT in this population of gold miners was very low.
- Clinical criteria appear sufficient for safe screening before and monitoring during isoniazid preventive therapy.
- IPT is a safe and potentially beneficial intervention for TB control in high-risk occupational settings.
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