Abstract

WHO information note indicates that isoniazid preventive therapy (IPT) is generally safe with little risk of hepatotoxicity. However, when the policy of IPT for HIV patients was introduced in Eritrea, frequent IPT‐associated hepatotoxicity and fatality have been reported to the Pharmacovigilance Centre. The aim of the study is to assess the causal association of IPT and hepatotoxicity and identify possible risk factors in patients on Highly Active Anti‐retroviral Therapy (HAART). This is a case series assessment of spontaneously reported cases to the Eritrean Pharmacovigilance Centre. Data extracted from VigiFlow (reported between 2014 and 2016) were exported to excel spread sheet for descriptive and qualitative analysis. Naranjo probability scale and Austin Bradford‐Hill criteria were used to assess causality. The P‐Method was used to assess preventability. A total of 31 of cases of hepatotoxicity related to IPT were retrieved. Majority (80.6%) of the cases were marked as “serious” due to life‐threatening situation (n = 15), hospitalization (n = 6), and death (n = 4). Baseline liver function test was normal in 61.3% and hepatitis B and C infections were ruled out in 77.4%. IPT was discontinued in 26 cases and reaction abated in 22 of them. Causality assessment using Austin Bradford‐Hill criteria found that the association was strong, consistent and specific with a plausible temporal relationship and biological mechanism. IPT‐associated hepatotoxicity that led to treatment interruption and death was observed in patients on HAART in Eritrea. Hence, close laboratory monitoring of patients is recommended to minimize the risk.

Highlights

  • Tuberculosis (TB) is the leading cause of death in patients infected with human immunodeficiency virus (HIV) in economically poor settings.[1]

  • In the period of June 2014 to June 2016, a total of 60 hepatotoxicity cases were spontaneously reported to the Eritrean Pharmacovigilance Centre with 31 of them related to isoniazid preventive therapy (IPT) in patients on highly active anti‐retroviral therapy (HAART)

  • Liver Function Test (LFT) baseline during the initiation of IPT was normal in 19 cases and unknown in 12 cases

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Summary

Introduction

Tuberculosis (TB) is the leading cause of death in patients infected with HIV in economically poor settings.[1]. Coinfection worsens the prognosis of HIV infection by increasing viral replication[3,4,5] and may result in subsequent immune suppression[6] and a higher risk of acquiring other, potentially lethal, opportunistic infections.[7] To mitigate this risk, WHO recommended countries to introduce isoniazid preventive therapy (IPT), INH 300 mg daily for 6 months, for people living with HIV8 aimed at preventing and reducing incidences of TB. Following the introduction of IPT in patients taking highly active anti‐retroviral therapy (HAART), some studies reported little risk of hepatotoxicity ranging from 0.07% to 1.9% without fatal outcomes.[19,20,21,22] Considering the low risks of INH‐induced hepatotoxicity, neither the WHO nor the Eritrean national IPT guidelines recommend routine baseline liver function test (LFT) for IPT.[23,24].

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