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

Autor: Roberta Gagliardini, Alessandro Cozzi-Lepri, Andrea Mariano, Fabrizio Taglietti, Alessandra Vergori, Amina Abdeddaim, Francesco Di Gennaro, Valentina Mazzotta, Alessandra Amendola, Giampiero D’Offizi, Fabrizio Palmieri, Luisa Marchioni, Pierluca Piselli, Chiara Agrati, Emanuele Nicastri, Maria Rosaria Capobianchi, Nicola Petrosillo, Giuseppe Ippolito, Francesco Vaia, Enrico Girardi, Andrea Antinori
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Frontiers in Pharmacology, Vol 12 (2021)
Druh dokumentu: article
ISSN: 1663-9812
DOI: 10.3389/fphar.2021.621676
Popis: Objectives: 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).Methods: 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.Primary endpoint: 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.Results: 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.Conclusion: 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.
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