Abstract: International Journal of Antimicrobial Agents 56 (2020) 106224 Contents lists available at ScienceDirect International Journal of Antimicrobial Agents journal homepage: www.elsevier.com/locate/ijantimicag Post-exposure prophylaxis with hydroxychloroquine for the prevention of COVID-19, a myth or a reality? The PEP-CQ Study Deba Prasad Dhibar a,∗, Navneet Arora a, Arpit Kakkar a, Neeraj Singla a, Ritin Mohindra a, Vikas Suri a, Ashish Bhalla a, Navneet Sharma a, Mini P. Singh b, Ajay Prakash c, Lakshmi PVM d, Bikash Medhi c a Department of Internal Medicine, PGIMER, Chandigarh, India Department of Virology, PGIMER, Chandigarh, India c Department of Pharmacology, PGIMER, Chandigarh, India d Community Medicine and School of Public Health, PGIMER, Chandigarh, India b a r t i c l e i n f o Article history: Received 26 August 2020 Accepted 1 November 2020 Keywords: Hydroxychloroquine Post-exposure prophylaxis COVID-19 SARS-CoV-2 Pandemic Prevention a b s t r a c t Many drugs have been tried for the treatment/prevention of COVID-19 with limited success. Direct household contacts of COVID-19 patients are at highest risk for SARS-CoV-2 infection. Hydroxychloroquine (HCQ) has been tried against COVID-19 owing to its in vitro virucidal action against SARS-CoV-2, but the role of HCQ as post-exposure prophylaxis (PEP) remains inconclusive. In this open-label, controlled clinical trial, asymptomatic individuals who had direct contact with laboratory-confirmed COVID-19 cases or had undertaken international travel in the last 2 weeks were offered HCQ prophylaxis and assigned to PEP (n = 132) or control (n = 185) group. The PEP group received HCQ 800 mg on Day 1 followed by 400 mg once weekly for 3 weeks. Both groups undertook home quarantine for 2 weeks along with social distancing and personal hygiene. Over 4-week follow-up, 50/317 participants (15.8%) had new-onset COVID19. The incidence of COVID-19 was significantly (P = 0.033) lower in the PEP (14/132; 10.6%) compared to the control (36/185; 19.5%) group (total absolute risk reduction, –8.9% points). The NNT to prevent the occurrence of 1 COVID-19 case was 12. Overall relative risk was 0.59 (95% CI 0.33–1.05). Compliance was good. The most common adverse event was epigastric discomfort with burning sensation (three participants), with no serious adverse events. PEP with HCQ has the potential for the prevention of COVID-19 in at-risk individuals. Until definitive therapy is available, continuing PEP with HCQ may be considered in suitable at-risk individuals. Further randomised clinical trials with larger samples are required for better evaluation of HCQ as PEP for COVID-19 prevention. © 2020 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.