AUTHOR=Gagliardini Roberta , Cozzi-Lepri Alessandro , Mariano Andrea , Taglietti Fabrizio , Vergori Alessandra , Abdeddaim Amina , Di Gennaro Francesco , Mazzotta Valentina , Amendola Alessandra , D’Offizi Giampiero , Palmieri Fabrizio , Marchioni Luisa , Piselli Pierluca , Agrati Chiara , Nicastri Emanuele , Capobianchi Maria Rosaria , Petrosillo Nicola , Ippolito Giuseppe , Vaia Francesco , Girardi Enrico , Antinori Andrea 

TITLE=No Efficacy of the Combination of Lopinavir/Ritonavir Plus Hydroxychloroquine Versus Standard of Care in Patients Hospitalized With COVID-19: A Non-Randomized Comparison

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.621676

DOI=10.3389/fphar.2021.621676

ISSN=1663-9812

ABSTRACT=<p><bold>Objectives:</bold> No specific treatment has been approved for COVID-19. Lopinavir/ritonavir (LPV/r) and hydroxychloroquine (HCQ) have been used with poor results, and a trial showed advantages of combined antiviral therapy vs. single antivirals. The aim of the study was to assess the effectiveness of the combination of antivirals (LPV/r and HCQ) or their single use in COVID-19 hospitalized patients vs. standard of care (SoC).</p><p><bold>Methods:</bold> Patients ≥18 years with SARS-CoV-2 infection, defined as positive RT-PCR from nasal/oropharyngeal (NP/OP) swab or positive serology, admitted at L. Spallanzani Institute (Italy) were included.</p><p><bold>Primary endpoint:</bold> time to invasive ventilation/death. Secondary endpoint: time to two consecutive negative SARS-CoV-2 PCRs in NP/OP swabs. In order to control for measured confounders, a marginal Cox regression model with inverse probability weights was used.</p><p><bold>Results:</bold> A total of 590 patients were included in the analysis: 36.3% female, 64 years (IQR 51–76), and 91% with pneumonia. Cumulative probability of invasive ventilation/death at 14 days was 21.2% (95% CI 17.6, 24.7), without difference between SOC, LPV/r, hydroxychloroquine, HCQ + LPV/r, and SoC. The risk of invasive ventilation/death in the groups appeared to vary by baseline ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2). Overall cumulative probability of confirmed negative nasopharyngeal swabs at 14 days was 44.4% (95% CI 38.9, 49.9), without difference between groups.</p><p><bold>Conclusion:</bold> In this retrospective analysis, we found no difference in the rate of invasive ventilation/death or viral shedding by different strategies, as in randomized trials performed to date. Moreover, even the combination HCQ + LPV/r did not show advantages vs. SoC.</p>