Case Report

Case report: Emergence of dolutegravir resistance in a patient on second-line antiretroviral therapy

Kairoonisha Mahomed, Carole L. Wallis, Liezl Dunn, Shavani Maharaj, Gary Maartens, Graeme Meintjes
Southern African Journal of HIV Medicine | Vol 21, No 1 | a1062 | DOI: https://doi.org/10.4102/sajhivmed.v21i1.1062 | © 2020 Kairoonisha Mahomed, Carole L. Wallis, Liezl Dunn, Shavani Maharaj, Gary Maartens, Graeme Meintjes | This work is licensed under CC Attribution 4.0
Submitted: 19 December 2019 | Published: 02 July 2020

About the author(s)

Kairoonisha Mahomed, Private practice, Johannesburg, South Africa
Carole L. Wallis, Department of Molecular Pathology, BARC-SA and Lancet Laboratories, Johannesburg, South Africa
Liezl Dunn, Aid for AIDS Management (Pty) Ltd, Cape Town, South Africa
Shavani Maharaj, Aid for AIDS Management (Pty) Ltd, Cape Town, South Africa
Gary Maartens, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
Graeme Meintjes, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa


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Abstract

Introduction: The integrase strand transfer inhibitor dolutegravir (DTG) has a high genetic barrier to resistance. Only rare cases of resistance to DTG have been reported when it is used as a component of antiretroviral therapy regimens in treatment-experienced patients unless there was prior use of a first-generation integrase inhibitor.

Patient presentation: A 38-year-old woman diagnosed with tuberculosis was switched to a second-line antiretroviral regimen of zidovudine, lamivudine and dolutegravir 50 mg 12-hourly together with rifampicin-based TB treatment. Based on treatment history and a previous resistance test there was resistance to lamivudine but full susceptibility to zidovudine. The patient did not suppress her viral load on this regimen and later admitted to only taking dolutegravir 50 mg in the morning because of insomnia.

Management and outcome: A second resistance test was performed which showed intermediate level of resistance to dolutegravir. Her regimen was changed to tenofovir, emtricitabine and ritonavir-boosted atazanavir with rifabutin replacing rifampicin for the remainder of her TB treatment. She achieved viral suppression on this regimen.

Conclusion: To our knowledge this is the first case report from South Africa of emergent dolutegravir resistance in a treatment-experienced, integrase inhibitor-naïve patient. Factors that may have contributed to resistance emergence in this patient were that there was only one fully active nucleoside reverse transcriptase inhibitor in the regimen and lower exposure to dolutegravir because of the reduced dosing frequency while on rifampicin.


Keywords

HIV drug resistance; antiretroviral therapy; regimens; dolutegravir; rifampicin

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