Introduction

Protease inhibitors such as lopinavir and darunavir combined with ritonavir and norvir, respectively, were repurposed drugs for the treatment of COVID-19. Although lopinavir-ritonavir (LPV/r) and darunavir-norvir (DRV/n) showed in vitro effectiveness against COVID-19, subsequent randomized controlled trials failed to demonstrate the benefit.

Aims Our aim was to compare the efficacy of LPV/r versus DRV/n in COVID-19 patients admitted to a tertiary center in Romania.

Methods

Clinical data records from 417 patients hospitalized were analyzed. Kaplan-Meier and Cox proportional hazards regression analysis were conducted to compare in-hospital mortality and to assess the factors associated with clinical improvement or fatal outcome in the control (standard care), LPV/r and DRV/n groups.

Results

Although at day 10 more patients showed improvement with LPV/r and DRV/n (p=0.03 and 0.01, respectively), only LPV/r was associated with improved survival compared to control (p=0.05). In our cohort, variables associated with mortality were: male gender (HR: 3.63, p=0.02), diabetes (HR:2.49, p=0.03), <90% O2 saturation at admission (HR:5.23, p<0.01), high blood glucose level (HR:3.68, p=0.01), age (HR:1.04, p=0.02) and >25% lesion extension on chest CT (HR:2.28, p=0.03). Subgroup analyses revealed that LPV/r showed survival benefits in patients without arterial hypertension (HR:0.07, p=0.02), diabetes (HR:0.23, p=0.04), or oxygen therapy (HR:0.18, p=0.05), and with all grades of lesions extension on chest CT, especially with the grade of >25% (HR:0.35, p=0.05).

Conclusion LPV/r, but not DRV/n demonstrated survival benefits in patients hospitalized for COVID-19 in this observational study.