Efficacy and Safety of Atazanavir/Ritonavir versus Lopinavir/Ritonavir in Hospitalized COVID-19 Patients: A Randomized Clinical Trial

Abstract

While several antivirals have been considered among the candidate repurposed drugs against SARS-CoV-2 infection, limited evidence exists on Atazanavir/Ritonavir. Objectives This trial was designed to assess the efficacy of Atazanavir/Ritonavir compared to Lopinavir/Ritonavir, another antiretroviral drug investigated in the previous studies. Methods This randomized, double-blind clinical trial was conducted on hospitalized patients with laboratory or confirmed SARS CoV-2 infection. Patients were randomly assigned (1:1) to receive either Lopinavir/Ritonavir (200mg Lopinavir+50mg Ritonavir, twice a day) or Atazanavir/Ritonavir (300mg Atazanavir+100 mg Ritonavir, once a day) for up to 14 days during their admission along with the standard care. The primary endpoint was total all-cause death in all patients during the hospitalization period. Secondary outcomes included length of hospitalization. Results Out of 103 adults included in the analysis 54 and 49 were assigned to Atazanavir/Ritonavir and Lopinavir/Ritonavir groups, respectively. The occurrence of adverse effects, defined as symptoms attributed to the drugs which no longer appear upon the cessation of the drug, was higher for cardiac side effects in Atazanavir/Ritonavir group. No statistically significant difference was observed between the two groups in terms of the length of hospitalization. After adjustment for other covariates in the study, treatment with Atazanavir/ritonavir did not result in a significant reduction in mortality compared to treatment with Lopinavir/Ritonavir. Conclusion The efficacy of Atazanavir/Ritonavir in this preliminary study was not superior to Lopinavir/Ritonavir in reducing mortality and length of hospitalization in COVID-19 patients. However, the limited efficacy of both compounds does not support their use in primary care for COVID-19 patients.