Journal Article

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

Meintjes, Graeme, Maartens, Gary, Wallis, Carole L., Maharaj, Shavani, Dunn, Liezl, Mahomed, Kairoonisha

2020

Overview

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. 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. 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. 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.

• Publisher: African Online Scientific Information Systems (Pty) Ltd t/a AOSIS,AOSIS (Pty) Ltd,AOSIS,Southern African HIV Clinicians Society
• Subject: Anti-HIV agents / Antiretroviral drugs / Antiretroviral therapy / Atazanavir / Bictegravir / Biology / Care and treatment / Case Report / Diarrhea / DNA polymerases / Dolutegravir / Drug dosages / Drug therapy / Emtricitabine / Health aspects / Health Care Sciences & Services / Health Policy & Services / Highly active antiretroviral therapy / HIV / hiv drug resistance / Human immunodeficiency virus / Immunology / Insomnia / Integrase / Lamivudine / Mutation / Nucleoside reverse transcriptase inhibitors / Patients / regimens / Reverse transcriptase inhibitors / Rifabutin / rifampicin / Rifampin / Ritonavir / RNA-directed DNA polymerase / Sleep disorders / Tenofovir / Tuberculosis / Zidovudine