Review

. 2020 Sep;26(9):1339-1350.

doi: 10.1038/s41591-020-1022-1. Epub 2020 Sep 7.

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

Mohamed Abdel-Mohsen¹, Douglas Richman², Robert F Siliciano³, Michel C Nussenzweig⁴, Bonnie J Howell⁵, Javier Martinez-Picado^{6

7

8}, Nicolas Chomont⁹, Katharine J Bar¹⁰, Xu G Yu^{11

12}, Mathias Lichterfeld^{11

12}, Jose Alcami¹³, Daria Hazuda⁵, Frederic Bushman¹⁰, Janet D Siliciano³, Michael R Betts¹⁰, Adam M Spivak¹⁴, Vicente Planelles¹⁴, Beatrice H Hahn¹⁰, Davey M Smith², Ya-Chi Ho¹⁵, Maria J Buzon¹³, Christian Gaebler⁴, Mirko Paiardini^{16

17}, Qingsheng Li¹⁸, Jacob D Estes¹⁹, Thomas J Hope²⁰, Jay Kostman²¹, Karam Mounzer²¹, Marina Caskey⁴, Lawrence Fox²², Ian Frank¹⁰, James L Riley¹⁰, Pablo Tebas¹⁰, Luis J Montaner²³; BEAT-HIV Delaney Collaboratory to Cure HIV-1 infection

Collaborators, Affiliations

Collaborators

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

Affiliations

¹ The Wistar Institute, Philadelphia, PA, USA.
² VA San Diego Healthcare System and University of California, San Diego, CA, USA.
³ Johns Hopkins University, Baltimore, MD, USA.
⁴ The Rockefeller University, New York, NY, USA.
⁵ Merck & Co., Inc., Kenilworth, NJ, USA.
⁶ IrsiCaixa AIDS Research Institute, Badalona, Spain.
⁷ University of Vic-Central University of Catalonia (UVic-UCC), Vic, Spain.
⁸ Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain.
⁹ Université de Montréal, Montréal, Québec, Canada.
¹⁰ University of Pennsylvania, Philadelphia, PA, USA.
¹¹ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
¹² Brigham and Women's Hospital, Boston, MA, USA.
¹³ AIDS Immunopathogenesis Unit, Instituto de Salud Carlos III, Madrid and Infectious Diseases Unit, IBIDAPS, Hospital Clinic, University of Barcelona, Barcelona, Spain.
¹⁴ University of Utah, Salt Lake City, UT, USA.
¹⁵ Yale School of Medicine, New Haven, CT, USA.
¹⁶ Division of Microbiology and Immunology, Yerkes National Primate Research Center, and Emory University, Atlanta, GA, USA.
¹⁷ Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
¹⁸ School of Biological Sciences and Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE, USA.
¹⁹ Vaccine and Gene Therapy Institute and Oregon National Primate Research Center (ONPRC), Oregon Health and Science University (OHSU), Beaverton, OR, USA.
²⁰ Northwestern University, Chicago, IL, USA.
²¹ Jonathan Lax Center, Philadelphia FIGHT, Philadelphia, PA, USA.
²² Division of AIDS, NIAID, NIH, North Bethesda, MD, USA.
²³ The Wistar Institute, Philadelphia, PA, USA. montaner@wistar.org.

PMID: 32895573
PMCID: PMC7703694
DOI: 10.1038/s41591-020-1022-1

Review

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

Mohamed Abdel-Mohsen et al. Nat Med. 2020 Sep.

. 2020 Sep;26(9):1339-1350.

doi: 10.1038/s41591-020-1022-1. Epub 2020 Sep 7.

Authors

Collaborators

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

Affiliations

¹ The Wistar Institute, Philadelphia, PA, USA.
² VA San Diego Healthcare System and University of California, San Diego, CA, USA.
³ Johns Hopkins University, Baltimore, MD, USA.
⁴ The Rockefeller University, New York, NY, USA.
⁵ Merck & Co., Inc., Kenilworth, NJ, USA.
⁶ IrsiCaixa AIDS Research Institute, Badalona, Spain.
⁷ University of Vic-Central University of Catalonia (UVic-UCC), Vic, Spain.
⁸ Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain.
⁹ Université de Montréal, Montréal, Québec, Canada.
¹⁰ University of Pennsylvania, Philadelphia, PA, USA.
¹¹ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
¹² Brigham and Women's Hospital, Boston, MA, USA.
¹³ AIDS Immunopathogenesis Unit, Instituto de Salud Carlos III, Madrid and Infectious Diseases Unit, IBIDAPS, Hospital Clinic, University of Barcelona, Barcelona, Spain.
¹⁴ University of Utah, Salt Lake City, UT, USA.
¹⁵ Yale School of Medicine, New Haven, CT, USA.
¹⁶ Division of Microbiology and Immunology, Yerkes National Primate Research Center, and Emory University, Atlanta, GA, USA.
¹⁷ Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
¹⁸ School of Biological Sciences and Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE, USA.
¹⁹ Vaccine and Gene Therapy Institute and Oregon National Primate Research Center (ONPRC), Oregon Health and Science University (OHSU), Beaverton, OR, USA.
²⁰ Northwestern University, Chicago, IL, USA.
²¹ Jonathan Lax Center, Philadelphia FIGHT, Philadelphia, PA, USA.
²² Division of AIDS, NIAID, NIH, North Bethesda, MD, USA.
²³ The Wistar Institute, Philadelphia, PA, USA. montaner@wistar.org.

PMID: 32895573
PMCID: PMC7703694
DOI: 10.1038/s41591-020-1022-1

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.

PubMed Disclaimer

Conflict of interest statement

Competing interests:

BH, DH are employees of Merck & Co.; RFS is an inventor on a patent application on the IPDA filed by JHU and licensed to AccelevirDx (RFS holds no equity on AccelevirDx).

Figures

**Figure 1.**
The collective view of the BEAT-HIV Collaboratory on the priority for measuring HIV reservoir size, in blood and tissues, during HIV cure-related clinical trials.

See this image and copyright information in PMC

References

1. Chargin A, et al. Identification and characterization of HIV-1 latent viral reservoirs in peripheral blood. Journal of clinical microbiology 53, 60–66 (2015). - PMC - PubMed
1. Chun TW, et al. Early establishment of a pool of latently infected, resting CD4(+) T cells during primary HIV-1 infection. Proceedings of the National Academy of Sciences of the United States of America 95, 8869–8873 (1998). - PMC - PubMed
1. Wong JK, et al. Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Science 278, 1291–1295 (1997). - PubMed
1. Wandeler G, Johnson LF & Egger M Trends in life expectancy of HIV-positive adults on antiretroviral therapy across the globe: comparisons with general population. Current opinion in HIV and AIDS 11, 492–500 (2016). - PMC - PubMed
1. Biggar RJ, Chaturvedi AK, Goedert JJ, Engels EA & Study HACM AIDS-related cancer and severity of immunosuppression in persons with AIDS. Journal of the National Cancer Institute 99, 962–972 (2007). - PubMed

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

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

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Conflict of interest statement

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References

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