Hydroxychloroquine as Postexposure Prophylaxis to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Type Journal Article Author Ruanne V. Barnabas Author Elizabeth R. Brown Author Anna Bershteyn Author Helen C. Stankiewicz Karita Author Christine Johnston Author Lorna E. Thorpe Author Angelica Kottkamp Author Kathleen M. Neuzil Author Miriam K. Laufer Author Meagan Deming Author Michael K. Paasche-Orlow Author Patricia J. Kissinger Author Alfred Luk Author Kristopher Paolino Author Raphael J. Landovitz Author Risa Hoffman Author Torin T. Schaafsma Author Meighan L. Krows Author Katherine K. Thomas Author Susan Morrison Author Harald S. Haugen Author Lara Kidoguchi Author Mark Wener Author Alexander L. Greninger Author Meei-Li Huang Author Keith R. Jerome Author Anna Wald Author Connie Celum Author Helen Y. Chu Author Jared M. Baeten URL https://www.acpjournals.org/doi/10.7326/M20-6519 Publication Annals of Internal Medicine ISSN 0003-4819 Date 08/12/2020 Extra Publisher: American College of Physicians Journal Abbr Ann Intern Med DOI 10.7326/M20-6519 Library Catalog acpjournals.org (Atypon) Abstract Background: Effective 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. Objective: To test hydroxychloroquine as postexposure prophylaxis for SARS-CoV-2 infection. Design: Household-randomized, double-blind, controlled trial of hydroxychloroquine postexposure prophylaxis. (ClinicalTrials.gov: NCT04328961) Setting: National U.S. multicenter study. Participants: Close contacts recently exposed (<96 hours) to persons with diagnosed SARS-CoV-2 infection. Intervention: Hydroxychloroquine (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. Measurements: Participants 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. Results: Between 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).