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. 2021 Apr 22:12:621676.
doi: 10.3389/fphar.2021.621676. eCollection 2021.

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

Roberta Gagliardini  1 , Alessandro Cozzi-Lepri  2 , Andrea Mariano  1 , Fabrizio Taglietti  1 , Alessandra Vergori  1 , Amina Abdeddaim  1 , Francesco Di Gennaro  1 , Valentina Mazzotta  1 , Alessandra Amendola  1 , Giampiero D'Offizi  1 , Fabrizio Palmieri  1 , Luisa Marchioni  1 , Pierluca Piselli  1 , Chiara Agrati  1 , Emanuele Nicastri  1 , Maria Rosaria Capobianchi  1 , Nicola Petrosillo  1 , Giuseppe Ippolito  1 , Francesco Vaia  1 , Enrico Girardi  1 , Andrea Antinori  1
Affiliations

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

Roberta Gagliardini et al. Front Pharmacol. .

Abstract

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.

Keywords: SARS-CoV-2; antivirals; drug repurposing; invasive ventilation; viral shedding.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Kaplan–Meier estimate of time to invasive ventilation/death–overall.
FIGURE 2
FIGURE 2
Kaplan–Meier estimate of time to invasive ventilation/death by treatment group in overall population (A) and in the strata of moderate patients (B).
FIGURE 3
FIGURE 3
Kaplan–Meier estimate of time to confirmed negative NP/OP swabs by treatment group.
FIGURE 4
FIGURE 4
Kaplan–Meier estimate of time to ventilation/death by treatment group.
See this image and copyright information in PMC

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