PHILADELPHIA -- (Sept. 7, 2020) -- Spearheaded by scientists at The Wistar Institute, top worldwide HIV researchers from the BEAT-HIV Martin Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy (BEAT-HIV Collaboratory) compiled the first comprehensive set of recommendations on how to best measure the size of persistent HIV reservoirs during cure-directed clinical studies. This perspective article was published today in Nature Medicine.
Cure-directed studies seek to control or eradicate HIV beyond current antiretroviral therapy (ART) which can only suppress but not eliminate HIV. Long-term viral persistence on ART continues to cause immune activation, chronic inflammation and progressive damage to multiple organs. Multiple cure-directed studies are underway worldwide but no consensus statement was available to prioritize and interpret the many strategies available today to measure persistent HIV on ART.
"Bringing together many of the original investigators who developed current assays used to measure HIV, the BEAT-HIV Collaboratory has now issued recommendations for priority in HIV measures as a guide for cure-directed studies," said Luis J. Montaner, D.V.M., D.Phil., the Herbert Kean, M.D., Family Professor and director of the HIV-1 Immunopathogenesis Laboratory at Wistar's Vaccine & Immunotherapy Center, co-leader of the Delaney Collaboratory and corresponding author on the article. "A major obstacle to eradication is the virus hiding in some compartments of the immune system where it's difficult to target and measure. The BEAT-HIV guidelines now provide specific information on the strengths and limitations of each assay available today."
The ability to accurately measure the size of these HIV reservoirs is critical when evaluating potential therapeutic strategies to cure HIV. It is also necessary for monitoring viral levels and guide ART interruption.
"We systematically reviewed the state of the science in the field and provided a collective and comprehensive view on which viral measurements to prioritize in clinical trials," said Mohamed Abdel-Mohsen, Ph.D., assistant professor in Wistar's Vaccine & Immunotherapy Center and one of the authors of the paper. "I think this is a crucial step to take the best advantage of the most valuable resource available to researchers in their quest to find a cure for HIV, the blood and tissue samples from people living with HIV who generously participate in the HIV cure-focused clinical trials all over the world."
In current HIV cure-directed studies in ART-suppressed people living with HIV, viral levels are monitored in peripheral blood cells obtained either by phlebotomy or leukapheresis (a laboratory procedure to separate white blood cells from whole blood) and biopsies from gut-associated lymphoid tissue or lymph nodes, though most trials only use peripheral blood because it is easier to collect.
In this work, the BEAT-HIV consortium compiled priority lists of the available assays and technologies to apply for each specimen type and collection method with the aim of aiding standardization of cure-directed trials.
Co-authors: Douglas Richman and David M Smith from VA San Diego Healthcare System and University of California, San Diego; Robert F. Siliciano and Janet D. Siliciano from Johns Hopkins University; Michel C. Nussenzweig, Christian Gaebler and Marina Caskey from The Rockefeller University; Bonnie Howell and Daria Hazuda from Merck & Co; Javier Martinez-Picado from IrsiCaixa AIDS Research Institute, Badalona, Spain, University of Vic - Central University of Catalonia, Spain and Catalan Institution for Research and Advanced Studies (ICREA), Spain; Nicolas Chomont from Université de Montréal, Canada; Katharine J Bar, Frederic Bushman, Michael R. Betts, Beatrice H. Hahn, Ian Frank, James L Riley, and Pablo Tebas from University of Pennsylvania; Xu G. Yu and Mathias Lichterfeld from Ragon Institute of MGH, MIT and Harvard and Brigham and Women's Hospital; Jose Alcami and Maria J. Buzon from Instituto de Salud Carlos III, Madrid and Infectious Diseases Unit, IBIDAPS, Hospital Clinic, University of Barcelona, Spain; Adam M. Spivak and Vicente Planelles from University of Utah; Ya-Chi Ho from Yale School of Medicine; Mirko Paiardini from Yerkes National Primate Research Center and Emory University; Qingsheng Li from School of Biological Sciences and Nebraska Center for Virology, University of Nebraska-Lincoln; Jacob D. Estes from Vaccine and Gene Therapy Institute and Oregon National Primate Research Center (ONPRC), Oregon Health and Science University; Thomas J Hope from Northwestern University; Jay Kostman and Karam Mounzer from Jonathan Lax Center, Philadelphia FIGHT; and Lawrence Fox from Division of AIDS, NIAID, NIH. All authors contributed to the writing and editing of the manuscript.
Wistar authors were supported by: National Health Institutes (NIH)-funded BEAT-HIV Martin Delaney Collaboratory to cure HIV-1 infection 1UM1Al126620; NIH grants R01 AI065279, U01 AI065279, R01 DA048728, R01 DA049666, R01 DK123733, R01 AG062383, R01NS117458, R21 AI143385, R21 AI129636, and R21 NS106970; Herbert Kean, M.D., Family Endowed Chair Professorship; the Robert I. Jacobs Fund of the Philadelphia Foundation; amfAR, The Foundation for AIDS Research impact grant 109840-65-RGRL; W.W. Smith Charitable Trust grant A1901; Wistar Cancer Center Support Grant P30 CA010815-49S2; and the Penn Center for AIDS Research P30 AI 045008.
Publication information: Recommendations for Measuring HIV Reservoir Size in Cure-directed Clinical Trials, Nature Medicine, 2020. Online publication.
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