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A Comparison of Adverse Drug Reaction Profiles in Patients on Antiretroviral and Antitubercular Treatment in Zimbabwe

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Abstract

Introduction

Few studies describe the adverse drug event profiles in patients simultaneously receiving antiretroviral and anti-tubercular medicines in resource-limited countries.

Objectives

To describe and compare the adverse drug reaction profiles in patients on highly active antiretroviral therapy only (HAART), HAART and isoniazid preventive therapy (HHART), and HAART and antitubercular treatment (ATTHAART).

Methods

We analysed individual case safety reports (ICSRs) for patients on antiretroviral therapy and antitubercular treatment submitted to the national pharmacovigilance centre during the targeted spontaneous reporting (TSR) programme from 1 September 2012 through 31 August 2016. All reports considered certain, probable or possible were included in the analysis.

Results

A total of 1076 ICSRs were included in the analysis. Most of the reports were from the HAART only group (n = 882; 82.0%), followed by patients on HHART (n = 132; 12.3%), and ATTHAART (n = 62; 5.7%). The ATTHAART (35.5%) and HHAART (34.1%) had a higher frequency of hepatic disorders than the HAART group (5.0%) (p < 0.0001). A higher frequency of rash was reported in the HHAART (35.6%) and HAART groups (29.4%) than the ATTHAART group (14.5%) (p = 0.011). Peripheral neuropathy occurred more frequently in the ATTHAART group (19.3%) than other groups (p = 0.001) while Stevens-Johnson syndrome (14.7%; p < 0.001), gynaecomastia (18.2%; p < 0.001), and lipodystrophy (4.5%; p = 0.012) occurred more frequently in the HAART group. The HHAART group was associated with a higher frequency of psychosis (4.5%; p = 0.002).

Conclusion

Antiretroviral therapy was associated with a higher frequency of Stevens-Johnson syndrome, gynaecomastia, and lipodystrophy. Co-administration of antiretroviral and antitubercular medicines was associated with a higher frequency of drug-induced liver injury and peripheral neuropathy. Similarly, co-administration of isoniazid preventive therapy and antiretroviral drugs was associated with a higher risk for psychosis. There is a need to carefully manage TB/HIV co-infected patients, due to the higher risk of adverse drug reactions which may lead to poor treatment adherence and outcomes.

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Acknowledgements

We gratefully acknowledge the Global Fund, WHO, WHO-Uppsala Monitoring Centre (UMC), UNICEF and MCAZ for providing financial support to strengthen pharmacovigilance for HIV and TB medicines in Zimbabwe and technical support for the VigiBase database. We also acknowledge the following: the Ministry of Health and Child Care ART and TB programmes, Directorate of Pharmacy Services, central hospitals, the district and/or provincial healthcare teams, and the Newlands Clinic, for their participation during the TSR programme and for collection of ADR reports. We also thank WHO, Mr Sten Olsson, Dr Shantil Pal for their contribution in the design and implementation of the TSR programme. We are also grateful to Dr Luther Gwaza and the Director General for MCAZ Gugulethu N Mahlangu, for their contribution in the design of the Targeted Spontaneous Reporting programme and their comments on the draft manuscript. We also acknowledge the contribution made by the Pharmacovigilance and Clinical Trials Committee during causality assessment of all reported ADRs.

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Authors and Affiliations

  1. Pharmacovigilance and Clinical Trials Division, Medicines Control Authority of Zimbabwe, 106 Baines Avenue, Harare, Zimbabwe

    Josiah T. Masuka, Precious Chipangura & Priscilla P. Nyambayo

  2. Schools of Pharmacy and Public Health, University of Washington, Box 357631, Seattle, WA, 98105, USA

    Andy Stergachis

  3. Department of Clinical Pharmacology, College of Health Sciences, University of Zimbabwe, P O Box A178, Avondale, Harare, Zimbabwe

    Star Khoza

Authors
  1. Josiah T. Masuka
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  2. Precious Chipangura
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  3. Priscilla P. Nyambayo
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  4. Andy Stergachis
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  5. Star Khoza
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Contributions

JTM was involved in the study design, collection and analysis of the data, and drafted the manuscript. PC was involved in the study design, collection and analysis of the data. PPN and SK were involved in the study design, analysis of the data, revised and critically reviewed the manuscript. AS critically reviewed and edited the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Star Khoza.

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Conflict of interest

All the authors declare no conflict of interest.

Funding

The targeted spontaneous reporting programme was funded through the Global Fund, Grant GF-OIG-13-012. Funding was also provided by WHO, UNICEF and MCAZ. The ADR reports used in this study were submitted during the targeted spontaneous reporting programme. However, no direct funding from the Global Fund grant and other donor partners was received in the conduct of this study and during preparation of the manuscript.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.

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Masuka, J.T., Chipangura, P., Nyambayo, P.P. et al. A Comparison of Adverse Drug Reaction Profiles in Patients on Antiretroviral and Antitubercular Treatment in Zimbabwe. Clin Drug Investig 38, 9–17 (2018). https://doi.org/10.1007/s40261-017-0579-z

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  • DOI: https://doi.org/10.1007/s40261-017-0579-z

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