Systematic review of the efficacy and safety of antiretroviral drugs against SARS, MERS or COVID‐19: initial assessment

Abstract

Introduction Several antiretroviral drugs are being considered the treatment of COVID‐19, the disease caused by a newly identified coronavirus, (SARS‐CoV‐2). We systematically reviewed the clinical outcomes of using antiretroviral drugs for the prevention and treatment of coronaviruses and planned clinical trials. Methods Three databases were screened from inception to 17 March 2020 for studies reporting clinical outcomes of patients with SARS, MERS, or COVID‐19 treated with antiretrovirals. Results From an initial screen of 413 titles, 1 randomized trial and 22 observational studies provided clinical outcome data on the use of antiretroviral drugs; most studies reported outcomes using LPV/r as treatment. Of the 20 observational studies reporting treatment outcomes, there were 3 studies among patients with SARS, 6 studies among patients with MERS, and 11 studies among patients with COVID‐19. In the randomized trial 99 patients with severe COVID‐19 illness were randomized to receive LPV/r (400mg/100mg twice a day) and 100 patients to standard of care for 14 days: LPV/r was not associated with a statistically significant difference in time to clinical improvement, although LPV/r given within 12 days of symptoms was associated with shorter time to clinical improvement; 28 day mortality was numerically lower in the LPV/r group (14/99) compared to the control group (25/100) but this difference was not statistically significant. The certainty of the evidence for the randomized trial was low. In the observational studies 2 out of 227 patients who received LPV/r died; the certainty of evidence was very low. Two studies reported a possible protective effect of LPV/r as post‐exposure prophylaxis. Again, the certainty of the evidence was very low due to uncertainty due to limited sample size. Conclusions On the basis of the available evidence it is uncertain whether LPV/r and other antiretrovirals improve clinical outcomes or prevent infection among patients at high risk of acquiring COVID‐19.