Virological Findings and Treatment Outcomes of Cases That Developed Dolutegravir Resistance in Malawi’s National HIV Treatment Program

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  • Kanise, Hope
    • Other Affiliation: Partners in Hope
  • van Oosterhout, Joep J.
    • Other Affiliation: Partners in Hope
  • Bisani, Pachawo
    • Other Affiliation: The Lighthouse Trust
  • Songo, John
    • Other Affiliation: Partners in Hope
  • Matola, Bilaal W.
    • Other Affiliation: Ministry of Health
  • Chipungu, Chifundo
    • Other Affiliation: Partners in Hope
  • Simon, Katherine
    • Other Affiliation: Baylor College of Medicine Children’s Foundation-Malawi
  • Cox, Carrie
    • Other Affiliation: Baylor College of Medicine Children’s Foundation-Malawi
  • Hosseinipour, Mina C.
    • Affiliation: School of Medicine, Department of Medicine
  • Sagno, Jean-Batiste
    • Other Affiliation: DREAM, Communion of St. Egidio
  • Hoffman, Risa M.
    • Other Affiliation: University of California, Los Angeles
  • Wallrauch, Claudia
    • Other Affiliation: The Lighthouse Trust
  • Phiri, Sam
    • Other Affiliation: Partners in Hope
  • Steegen, Kim
    • Other Affiliation: National Health Laboratory Service
  • Jahn, Andreas
    • Other Affiliation: Ministry of Health
  • Nyirenda, Rose
    • Other Affiliation: Ministry of Health
  • Heller, Tom
    • Other Affiliation: The Lighthouse Trust
Abstract
  • Millions of Africans are on dolutegravir-based antiretroviral therapy (ART), but few detailed descriptions of dolutegravir resistance and its clinical management exist. We reviewed HIV drug resistance (HIVDR) testing application forms submitted between June 2019 and October 2022, data from the national HIVDR database, and genotypic test results. We obtained standardized ART outcomes and virological results of cases with dolutegravir resistance, and explored associations with dolutegravir resistance among individuals with successful integrase sequencing. All cases were on two nucleoside reverse transcriptase inhibitors (NRTIs)/dolutegravir, and had confirmed virological failure, generally with prolonged viremia. Among 89 samples with successful integrase sequencing, 24 showed dolutegravir resistance. Dolutegravir resistance-associated mutations included R263K (16/24), E138K (7/24), and G118R (6/24). In multivariable logistic regression analysis, older age and the presence of high-level NRTI resistance were significantly associated with dolutegravir resistance. After treatment modification recommendations, four individuals (17%) with dolutegravir resistance died, one self-discontinued ART, one defaulted, and one transferred out. Of the 17 remaining individuals, 12 had follow-up VL results, and 11 (92%) were <1000 copies/mL. Twenty-four cases with dolutegravir resistance among 89 individuals with confirmed virological failure suggests a considerable prevalence in the Malawi HIV program. Successful management of dolutegravir resistance was possible, but early mortality was high. More research on the management of treatment-experienced individuals with dolutegravir resistance is needed.
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  • Article
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  • In Copyright
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  • Attribution 4.0 International
Journal title
  • Viruses
Journal volume
  • 16
Journal issue
  • 1
Page start
  • 29
Language
  • English
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  • 1999-4915
Publisher
  • Multidisciplinary Digital Publishing Institute (MDPI)

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