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HIV-1 diversity considerations in the application of the Intact Proviral DNA Assay (IPDA)

Author

Listed:
  • Natalie N. Kinloch

    (Simon Fraser University
    British Columbia Centre for Excellence in HIV/AIDS)

  • Yanqin Ren

    (Weill Cornell Medical College)

  • Winiffer D. Conce Alberto

    (Weill Cornell Medical College)

  • Winnie Dong

    (British Columbia Centre for Excellence in HIV/AIDS)

  • Pragya Khadka

    (Weill Cornell Medical College)

  • Szu Han Huang

    (Weill Cornell Medical College)

  • Talia M. Mota

    (Weill Cornell Medical College)

  • Andrew Wilson

    (George Washington University)

  • Aniqa Shahid

    (Simon Fraser University
    British Columbia Centre for Excellence in HIV/AIDS)

  • Don Kirkby

    (British Columbia Centre for Excellence in HIV/AIDS)

  • Marianne Harris

    (British Columbia Centre for Excellence in HIV/AIDS
    University of British Columbia)

  • Colin Kovacs

    (Maple Leaf Medical Clinic)

  • Erika Benko

    (Maple Leaf Medical Clinic)

  • Mario A. Ostrowski

    (University of Toronto)

  • Perla M. Rio Estrada

    (National Institute of Respiratory Diseases)

  • Avery Wimpelberg

    (Whitman Walker Health)

  • Christopher Cannon

    (Whitman Walker Health)

  • W. David Hardy

    (Whitman Walker Health)

  • Lynsay MacLaren

    (Whitman Walker Health)

  • Harris Goldstein

    (Albert Einstein College of Medicine)

  • Chanson J. Brumme

    (British Columbia Centre for Excellence in HIV/AIDS
    University of British Columbia)

  • Guinevere Q. Lee

    (Weill Cornell Medical College)

  • Rebecca M. Lynch

    (George Washington University)

  • Zabrina L. Brumme

    (Simon Fraser University
    British Columbia Centre for Excellence in HIV/AIDS)

  • R. Brad Jones

    (Weill Cornell Medical College
    George Washington University)

Abstract

The Intact Proviral DNA Assay (IPDA) was developed to address the critical need for a scalable method for intact HIV-1 reservoir quantification. This droplet digital PCR-based assay simultaneously targets two HIV-1 regions to distinguish genomically intact proviruses against a large background of defective ones, and its application has yielded insights into HIV-1 persistence. Reports of assay failures however, attributed to HIV-1 polymorphism, have recently emerged. Here, we describe a diverse North American cohort of people with HIV-1 subtype B, where the IPDA yielded a failure rate of 28% due to viral polymorphism. We further demonstrate that within-host HIV-1 diversity can lead the IPDA to underestimate intact reservoir size, and provide examples of how this phenomenon could lead to erroneous interpretation of clinical trial data. While the IPDA represents a major methodological advance, HIV-1 diversity should be addressed before its widespread adoption as a principal readout in HIV-1 remission trials.

Suggested Citation

  • Natalie N. Kinloch & Yanqin Ren & Winiffer D. Conce Alberto & Winnie Dong & Pragya Khadka & Szu Han Huang & Talia M. Mota & Andrew Wilson & Aniqa Shahid & Don Kirkby & Marianne Harris & Colin Kovacs &, 2021. "HIV-1 diversity considerations in the application of the Intact Proviral DNA Assay (IPDA)," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20442-3
    DOI: 10.1038/s41467-020-20442-3
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    Cited by:

    1. Xiaolei Wang & Eunice Vincent & Summer Siddiqui & Katherine Turnbull & Hong Lu & Robert Blair & Xueling Wu & Meagan Watkins & Widade Ziani & Jiasheng Shao & Lara A. Doyle-Meyers & Kasi E. Russell-Lodr, 2022. "Early treatment regimens achieve sustained virologic remission in infant macaques infected with SIV at birth," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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