Abstract: https://doi.org/10.1038/s41586-020-2558-4 Accelerated Article Preview W E I V E R P E L C I T R A D E T A R E L E C C A Hydroxychloroquine use against SARSCoV-2 infection in non-human primates Received: 30 April 2020 Accepted: 10 July 2020 Accelerated Article Preview Published online 22 July 2020 Cite this article as: Maisonnasse, P. et al. Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates. Nature https://doi.org/10.1038/ s41586-020-2558-4 (2020). Pauline Maisonnasse, Jérémie Guedj, Vanessa Contreras, Sylvie Behillil, Caroline Solas, Romain Marlin, Thibaut Naninck, Andres Pizzorno, Julien Lemaitre, Antonio Gonçalves, Nidhal Kahlaoui, Olivier Terrier, Raphael Ho Tsong Fang, Vincent Enouf, Nathalie Dereuddre-Bosquet, Angela Brisebarre, Franck Touret, Catherine Chapon, Bruno Hoen, Bruno Lina, Manuel Rosa Calatrava, Sylvie van der Werf, Xavier de Lamballerie & Roger Le Grand This is a PDF file of a peer-reviewed paper that has been accepted for publication. Although unedited, the content has been subjected to preliminary formatting. Nature is providing this early version of the typeset paper as a service to our authors and readers. The text and figures will undergo copyediting and a proof review before the paper is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply. Nature | www.nature.com Article Hydroxychloroquine use against SARSCoV-2 infection in non-human primates W E I V E R P E L C I T R A D E T A R E L E C C A https://doi.org/10.1038/s41586-020-2558-4 Received: 30 April 2020 Accepted: 10 July 2020 Published online: 22 July 2020 Pauline Maisonnasse1,11, Jérémie Guedj2,11, Vanessa Contreras1,11, Sylvie Behillil3,4,11, Caroline Solas5,11, Romain Marlin1,11, Thibaut Naninck1, Andres Pizzorno6, Julien Lemaitre1, Antonio Gonçalves2, Nidhal Kahlaoui1, Olivier Terrier6, Raphael Ho Tsong Fang1, Vincent Enouf3,4,10, Nathalie Dereuddre-Bosquet1, Angela Brisebarre3,4, Franck Touret8, Catherine Chapon1, Bruno Hoen9, Bruno Lina6,7, Manuel Rosa Calatrava6, Sylvie van der Werf3,4, Xavier de Lamballerie8 & Roger Le Grand1 ✉ COVID-19 has rapidly become a pandemic for which no antiviral drug or vaccine is yet available2–4. Several clinical studies are ongoing to evaluate the efficacy of repurposed drugs that have demonstrated antiviral efficacy in vitro. Among these candidates, hydroxychloroquine (HCQ) has been given to thousands of individuals worldwide but definitive evidence for HCQ efficacy in treatment of COVID-19 is still missing6,7,17,18. We evaluated the antiviral activity of HCQ both in vitro and in SARS-CoV-2-infected macaques. HCQ showed antiviral activity in African green monkey kidney cells (VeroE6) but not in a model of reconstituted human airway epithelium. In macaques, we tested different treatment strategies in comparison to placebo, before and after peak viral load, alone or in combination with azithromycin (AZTH). Neither HCQ nor HCQ+AZTH showed a significant effect on the viral load levels in any of the tested compartments. When the drug was used as a pre-exposure prophylaxis (PrEP), HCQ did not confer protection against acquisition of infection. Our findings do not support the use of HCQ, either alone or in combination with AZTH, as an antiviral treatment for COVID-19 in humans. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by initial mild..