Post-exposure prophylaxis with hydroxychloroquine for the prevention of COVID-19, a myth or a reality? The PEP-CQ Study

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 COVID-19. 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.