• Ruanne V Barnabas, Elizabeth R Brown, Anna Bershteyn, Helen C Stankiewicz Karita, Christine Johnston, Lorna E Thorpe, Angelica Kottkamp, Kathleen M Neuzil, Miriam K Laufer, Meagan Deming, Michael K Paasche-Orlow, Patricia J Kissinger, Alfred Luk, Kristopher Paolino, Raphael J Landovitz, Risa Hoffman, Torin T Schaafsma, Meighan L Krows, Katherine K Thomas, Susan Morrison, Harald S Haugen, Lara Kidoguchi, Mark Wener, Alexander L Greninger, Meei-Li Huang, Keith R Jerome, Anna Wald, Connie Celum, Helen Y Chu, Jared M Baeten, and Hydroxychloroquine COVID-19 PEP Study Team.
• University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington (R.V.B., E.R.B., C.J., A.L.G., K.R.J., A.W.).
• Ann. Intern. Med. 2021 Mar 1; 174 (3): 344-352.

BackgroundEffective prevention against coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently limited to nonpharmaceutical strategies. Laboratory and observational data suggested that hydroxychloroquine had biological activity against SARS-CoV-2, potentially permitting its use for prevention.ObjectiveTo test hydroxychloroquine as postexposure prophylaxis for SARS-CoV-2 infection.DesignHousehold-randomized, double-blind, controlled trial of hydroxychloroquine postexposure prophylaxis. (ClinicalTrials.gov: NCT04328961).SettingNational U.S. multicenter study.ParticipantsClose contacts recently exposed (<96 hours) to persons with diagnosed SARS-CoV-2 infection.InterventionHydroxychloroquine (400 mg/d for 3 days followed by 200 mg/d for 11 days) or ascorbic acid (500 mg/d followed by 250 mg/d) as a placebo-equivalent control.MeasurementsParticipants self-collected mid-turbinate swabs daily (days 1 to 14) for SARS-CoV-2 polymerase chain reaction (PCR) testing. The primary outcome was PCR-confirmed incident SARS-CoV-2 infection among persons who were SARS-CoV-2 negative at enrollment.ResultsBetween March and August 2020, 671 households were randomly assigned: 337 (407 participants) to the hydroxychloroquine group and 334 (422 participants) to the control group. Retention at day 14 was 91%, and 10 724 of 11 606 (92%) expected swabs were tested. Among the 689 (89%) participants who were SARS-CoV-2 negative at baseline, there was no difference between the hydroxychloroquine and control groups in SARS-CoV-2 acquisition by day 14 (53 versus 45 events; adjusted hazard ratio, 1.10 [95% CI, 0.73 to 1.66]; P > 0.20). The frequency of participants experiencing adverse events was higher in the hydroxychloroquine group than the control group (66 [16.2%] versus 46 [10.9%], respectively; P = 0.026).LimitationThe delay between exposure, and then baseline testing and the first dose of hydroxychloroquine or ascorbic acid, was a median of 2 days.ConclusionThis rigorous randomized controlled trial among persons with recent exposure excluded a clinically meaningful effect of hydroxychloroquine as postexposure prophylaxis to prevent SARS-CoV-2 infection.Primary Funding SourceBill & Melinda Gates Foundation.

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