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Recommendations for measuring HIV reservoir size in cure-directed clinical trials

Nature Medicine volume 26, pages 1339–1350 (2020)Cite this article

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Abstract

Therapeutic strategies are being clinically tested either to eradicate latent HIV reservoirs or to achieve virologic control in the absence of antiretroviral therapy. Attaining this goal will require a consensus on how best to measure the numbers of persistently infected cells with the potential to cause viral rebound after antiretroviral-therapy cessation in assessing the results of cure-directed strategies in vivo. Current measurements assess various aspects of the HIV provirus and its functionality and produce divergent results. Here, we provide recommendations from the BEAT-HIV Martin Delaney Collaboratory on which viral measurements should be prioritized in HIV-cure-directed clinical trials.

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Fig. 1: The collective view of the BEAT-HIV Collaboratory on the priorities for measuring HIV reservoir size in blood and tissues during HIV-cure-related clinical trials.

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Acknowledgements

This work was supported by the NIH-funded BEAT-HIV Martin Delaney Collaboratory to cure HIV-1 infection (1UM1Al126620). L.J.M. is also supported by NIH R01 AI065279, U01 AI065279, R01 DA048728, R01 DA049666, the Kean Family Professorship and the Philadelphia Foundation (Roberts I. Jacobs Fund). M.A.-M. is supported by NIH grants (R01 DK123733, R01 AG062383, R01NS117458, R21 AI143385, R21 AI129636 and R21 NS106970), The Foundation for AIDS Research (amfAR) impact grant 109840-65-RGRL, W.W. Smith Charitable Trust grant A1901, The Campbell Foundation, Mizutani Foundation for Glycoscience, Wistar Cancer Center Support grant P30 CA010815-49S2 and the Penn Center for AIDS Research (P30 AI 045008). M.J.B. is supported by The Miguel Servet program funded by the Spanish Health Institute Carlos III (CP17/00179). M.L. is supported by NIH grants AI117841, AI120008, AI124776, AI130005, AI122377 and AI135940. X.G.Y. is supported by NIH grants AI116228, AI078799, HL134539, AI125109 and DA047034. R.F.S. is supported by NIH grants UM1 AI126603, UM1 AI126620, UM1 AI12661 and P30 AI094189, the Howard Hughes Medical Institute and the Bill and Melinda Gates Foundation (OPP1115715). V.P. is supported by NIH grants R01 AI143567 and AI 124843. Y.-C.H. is supported by a Yale Top Scholar Award, a Rudolf J. Anderson Fellowship, NIH grants AI141009, DA047037, AI118402, P50 AI150464, P30 AI094189 and R37 AI14868, a W.W. Smith AIDS Research Grant, a Gilead AIDS Research Grant and a Gilead Research Scholar Grant. J.D.E. is supported by the NIH and Bill and Melinda Gates Foundation grants 75N93019C00070, AI133706, AI110164, AI141258, AI143411-01A1, AI149672, CA206466, DK119945, INV-002704, OD011092-60 and OPPO1108533. D.R. is supported by the NIH CARE Martin Delaney Collaboratory (1UM1AI126619 0), the UCSD NIH CFAR (AI306214), the Department of Veterans Affairs and the James B. Pendleton Charitable Trust. J.L.R. is supported by NIH grants U19AI117950, U19AI149680 and UM1AI126620.

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Authors and Affiliations

  1. The Wistar Institute, Philadelphia, PA, USA

    Mohamed Abdel-Mohsen, Luis J. Montaner, Mohamed Abdel-Mohsen & Luis J. Montaner

  2. VA San Diego Healthcare System and University of California, San Diego, CA, USA

    Douglas Richman, Davey M. Smith, Douglas Richman & Davey M. Smith

  3. Johns Hopkins University, Baltimore, MD, USA

    Robert F. Siliciano, Janet D. Siliciano, Robert F. Siliciano & Janet D. Siliciano

  4. The Rockefeller University, New York, NY, USA

    Michel C. Nussenzweig, Christian Gaebler, Marina Caskey, Michel C. Nussenzweig, Christian Gaebler & Marina Caskey

  5. Merck & Co., Inc., Kenilworth, NJ, USA

    Bonnie J. Howell, Daria Hazuda, Bonnie J. Howell & Daria Hazuda

  6. IrsiCaixa AIDS Research Institute, Badalona, Spain

    Javier Martinez-Picado & Javier Martinez-Picado

  7. University of Vic–Central University of Catalonia (UVic-UCC), Vic, Spain

    Javier Martinez-Picado & Javier Martinez-Picado

  8. Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain

    Javier Martinez-Picado & Javier Martinez-Picado

  9. Université de Montréal, Montréal, Québec, Canada

    Nicolas Chomont & Nicolas Chomont

  10. University of Pennsylvania, Philadelphia, PA, USA

    Katharine J. Bar, Frederic Bushman, Michael R. Betts, Beatrice H. Hahn, Ian Frank, James L. Riley, Pablo Tebas, Katharine J. Bar, Frederic Bushman, Michael R. Betts, Beatrice H. Hahn, Ian Frank, James L. Riley & Pablo Tebas

  11. Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA

    Xu G. Yu, Mathias Lichterfeld, Xu G. Yu & Mathias Lichterfeld

  12. Brigham and Women’s Hospital, Boston, MA, USA

    Xu G. Yu, Mathias Lichterfeld, Xu G. Yu & Mathias Lichterfeld

  13. AIDS Immunopathogenesis Unit, Instituto de Salud Carlos III, Madrid and Infectious Diseases Unit, IBIDAPS, Hospital Clinic, University of Barcelona, Barcelona, Spain

    Jose Alcami, Maria J. Buzon, Jose Alcami & Maria J. Buzon

  14. University of Utah, Salt Lake City, UT, USA

    Adam M. Spivak, Vicente Planelles, Adam M. Spivak & Vicente Planelles

  15. Yale School of Medicine, New Haven, CT, USA

    Ya-Chi Ho & Ya-Chi Ho

  16. Division of Microbiology and Immunology, Yerkes National Primate Research Center, and Emory University, Atlanta, GA, USA

    Mirko Paiardini & Mirko Paiardini

  17. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA

    Mirko Paiardini & Mirko Paiardini

  18. School of Biological Sciences and Nebraska Center for Virology, University of Nebraska–Lincoln, Lincoln, NE, USA

    Qingsheng Li & Qingsheng Li

  19. Vaccine and Gene Therapy Institute and Oregon National Primate Research Center (ONPRC), Oregon Health and Science University (OHSU), Beaverton, OR, USA

    Jacob D. Estes & Jacob D. Estes

  20. Northwestern University, Chicago, IL, USA

    Thomas J. Hope & Thomas J. Hope

  21. Jonathan Lax Center, Philadelphia FIGHT, Philadelphia, PA, USA

    Jay Kostman, Karam Mounzer, Jay Kostman & Karam Mounzer

  22. Division of AIDS, NIAID, NIH, North Bethesda, MD, USA

    Lawrence Fox & Lawrence Fox

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  1. Mohamed Abdel-Mohsen
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  2. Douglas Richman
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Consortia

The BEAT-HIV Delaney Collaboratory to Cure HIV-1 infection

  • Mohamed Abdel-Mohsen
  • , Douglas Richman
  • , Robert F. Siliciano
  • , Michel C. Nussenzweig
  • , Bonnie J. Howell
  • , Javier Martinez-Picado
  • , Nicolas Chomont
  • , Katharine J. Bar
  • , Xu G. Yu
  • , Mathias Lichterfeld
  • , Jose Alcami
  • , Daria Hazuda
  • , Frederic Bushman
  • , Janet D. Siliciano
  • , Michael R. Betts
  • , Adam M. Spivak
  • , Vicente Planelles
  • , Beatrice H. Hahn
  • , Davey M. Smith
  • , Ya-Chi Ho
  • , Maria J. Buzon
  • , Christian Gaebler
  • , Mirko Paiardini
  • , Qingsheng Li
  • , Jacob D. Estes
  • , Thomas J. Hope
  • , Jay Kostman
  • , Karam Mounzer
  • , Marina Caskey
  • , Lawrence Fox
  • , Ian Frank
  • , James L. Riley
  • , Pablo Tebas
  •  & Luis J. Montaner

Contributions

All authors contributed to the writing and editing of the manuscript.

Corresponding author

Correspondence to Luis J. Montaner.

Ethics declarations

Competing interests

B.J.H. and D.H. are employees of Merck & Co.; R.F.S. is an inventor on a patent application on the IPDA filed by Johns Hopkins University and licensed to AccelevirDx (R.F.S. holds no equity in AccelevirDx).

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Abdel-Mohsen, M., Richman, D., Siliciano, R.F. et al. Recommendations for measuring HIV reservoir size in cure-directed clinical trials. Nat Med 26, 1339–1350 (2020). https://doi.org/10.1038/s41591-020-1022-1

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