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Completion Rates and Hepatotoxicity of Isoniazid Preventive Therapy Among Children Living with HIV/AIDS: Findings and Implications in Northwestern Nigeria

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Abstract

Background and Objective

Childhood tuberculosis remains a global public health threat despite being preventable and curable. Childhood tuberculosis prevention using strategies including isoniazid preventive therapy is evidence based and cost effective. This study aimed to determine the isoniazid preventive therapy completion rate and predictors of hepatotoxicity of isoniazid among children who sought human immunodeficiency virus (HIV)/acquired immune deficiency syndrome care in public hospitals in Sokoto, Nigeria.

Methods

This was a 4-year (2016–19) retrospective chart review of 429 paediatric patients with HIV/acquired immune deficiency syndrome aged ≤18 years, accessing isoniazid preventive therapy from Usmanu Danfodiyo University Teaching Hospital and Specialist Hospital, Sokoto, Nigeria. The study commenced in January 2020 and lasted for 6 months. Regression models were used to determine predictors of the isoniazid preventive therapy completion rate and the development of hepatotoxicity.

Results

Of the 429 HIV-infected children initiated on isoniazid preventive therapy, 244 (56.9%) successfully completed isoniazid preventive therapy. Young age and low socioeconomic status were the strongest predictors of the isoniazid preventive therapy completion rate. Only 37 (18.0%; 37/205) were found to have their alanine transaminase raised to a grade 1 level (47.5–95.0 U/L) with the median (interquartile range) being 71 (53–87) U/L. Advanced HIV (HIV clinical stages 3 and 4) predicted isoniazid-induced hepatotoxicity.

Conclusions

The isoniazid preventive therapy completion rate was sub-optimal and the incidence rate of developing grade 1 liver injury was low among the study cohort. We recommend community-appropriate and tailored strategies to promote the isoniazid preventive therapy completion rate and that their liver enzymes be monitored especially for children with advanced HIV disease.

Plain Language Summary

The burden of childhood tuberculosis continues to remain unacceptably high in developing countries despite the preventability and curability of the disease. Tuberculosis and human immunodeficiency virus (HIV) often coexist and impact each other and thus form a highly lethal partnership. Consequently, measures such as isoniazid preventive therapy (IPT) that can prevent such coexistence is highly warranted. However, low uptake and completion rate, and hepatotoxicity threaten the beneficial effects of IPT. The study investigated the completion rate of a 6-month course of IPT among HIV/acquired immune deficiency syndrome-infected children on antiretroviral drugs and the predictors of hepatotoxicity of the IPT. The 4-year retrospective chart review revealed a less-than-adequate IPT completion rate of 56.9% (244/429) that was predicted by young age (≤10 years) and low socioeconomic status of the children. A grade 1 level elevation of alanine transaminase (47.5–95.0 U/L: mild hepatotoxicity) was also recorded among 18.0% (37/205) of the children and this was predicted by HIV clinical stage. The alanine transaminase levels of the remaining children (82.0%; 168/205) were within the normal range. Interventions designed to improve the IPT completion rate and periodic measurement of alanine transaminase for those with advanced HIV (HIV clinical stages 3 and 4) were recommended.

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Authors and Affiliations

  1. Department of Clinical Pharmacy and Pharmacy Practice, Usmanu Danfodiyo University, Sokoto, Nigeria

    Ibrahim Abayomi Ogunyinka & Yusuf Hassan Wada

  2. Department of Paediatrics, Specialist Hospital, Sokoto, Nigeria

    Tajudeen Bolajoko

  3. Department of Paediatrics, Usmanu Danfodiyo University Teaching Hospital, Sokoto, Nigeria

    Yusuf Tahir

  4. Department of Pharmacology, Therapeutics and Toxicology, College of Medicine, Lagos State University, Ikeja, Lagos, Nigeria

    Kazeem Adeola Oshikoya

  5. Society for Family Health, Nigeria, Abuja, Nigeria

    Yusuf Hassan Wada

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  1. Ibrahim Abayomi Ogunyinka
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Correspondence to Ibrahim Abayomi Ogunyinka.

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The authors have no relevant affiliations or financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in this article. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Ethics approval

Approval was sought and received from the Health Research and Ethics Committees of Usmanu Danfodiyo University Teaching Hospital (UDUTH/HREC/2019/No.845) and Specialist Hospital (SHS/SUB/133/VOL.1), Sokoto, Nigeria. The procedures used in this study adhere to the tenets of the Declaration of Helsinki and the ethical standards of the relevant national guidelines on human experimentation.

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The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.

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OIA and OKA were involved in the conception and design of this work. All authors were involved with data collection. OIA undertook the literature search and the first draft of the work. All authors approved the final version of the manuscript submitted for publication consideration.

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Ogunyinka, I.A., Wada, Y.H., Bolajoko, T. et al. Completion Rates and Hepatotoxicity of Isoniazid Preventive Therapy Among Children Living with HIV/AIDS: Findings and Implications in Northwestern Nigeria. Drugs Ther Perspect 38, 455–466 (2022). https://doi.org/10.1007/s40267-022-00946-2

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