Journal article

Multiply spliced HIV RNA is a predictive measure of virus production ex vivo and in vivo following reversal of HIV latency

Jennifer M Zerbato, Georges Khoury, Wei Zhao, Matthew J Gartner, Rachel D Pascoe, Ajantha Rhodes, Ashanti Dantanarayana, Megan Gooey, Jenny Anderson, Peter Bacchetti, Steven G Deeks, James McMahon, Michael Roche, Thomas A Rasmussen, Damian FJ Purcell, Sharon R Lewin

EBIOMEDICINE | ELSEVIER | Published : 2021

Abstract

BACKGROUND: One strategy being pursued to clear latently infected cells that persist in people living with HIV (PLWH) on antiretroviral therapy (ART) is to activate latent HIV infection with a latency reversing agent (LRA). Surrogate markers that accurately measure virus production following an LRA are needed. METHODS: We quantified cell-associated unspliced (US), multiply spliced (MS) and supernatant (SN) HIV RNA by qPCR from total and resting CD4+ T cells isolated from seven PLWH on ART before and after treatment ex vivo with different LRAs, including histone deacetylase inhibitors (HDACi). MS and plasma HIV RNA were also quantified from PLWH on ART (n-11) who received the HDACi panobinost..

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Grants

Awarded by National Health and Medical Research Council (NHMRC) of Australia


Awarded by National Institutes of Health Delaney AIDS Research Enterprise (DARE)


Funding Acknowledgements

We would like to thank the Department of Infectious Diseases at the Alfred Hospital and the Lewin/Cameron Clinical Research Group at the Peter Doherty Institute for providing and processing the leukapheresis samples. We would like to thank the HIV Characterisation Laboratory, Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Doherty Institute for quantification of supernatant HIV RNA. This work was supported by the National Health and Medical Research Council (NHMRC) of Australia program grant GNT1149990 (SRL, DFJP), and project grant GNT1129320 (DFJP), and practitioner fellowship to SRL (GNT1135851) and the National Institutes of Health Delaney AIDS Research Enterprise (DARE) to find a cure collaboratory (UM1AI126611-01).