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. 2021 Mar;93(3):1421-1427.
doi: 10.1002/jmv.26407. Epub 2020 Sep 28.

Early administration of lopinavir/ritonavir plus hydroxychloroquine does not alter the clinical course of SARS-CoV-2 infection: A retrospective cohort study

Andrea Giacomelli  1   2 , Gabriele Pagani  1   2 , Anna L Ridolfo  1 , Letizia Oreni  2 , Federico Conti  1   2 , Laura Pezzati  1   2 , Lucia Bradanini  1   2 , Giacomo Casalini  1   2 , Cinzia Bassoli  1   2 , Valentina Morena  1   2 , Simone Passerini  1 , Giuliano Rizzardini  1   3 , Chiara Cogliati  4 , Elisa Ceriani  4 , Riccardo Colombo  5 , Stefano Rusconi  1   2 , Cristina Gervasoni  1 , Dario Cattaneo  6 , Spinello Antinori  1   2 , Massimo Galli  1   2
Affiliations

Early administration of lopinavir/ritonavir plus hydroxychloroquine does not alter the clinical course of SARS-CoV-2 infection: A retrospective cohort study

Andrea Giacomelli et al. J Med Virol. 2021 Mar.

Abstract

As it has been shown that lopinavir (LPV) and hydroxychloroquine (HCQ) have in vitro activity against coronaviruses, they were used to treat COVID-19 during the first wave of the epidemic in Lombardy, Italy. To compare the rate of clinical improvement between those who started LPV/ritonavir (LPV/r)+HCQ within 5 days of symptom onset (early treatment, ET) and those who started later (delayed treatment, DT). This was a retrospective intent-to-treat analysis of the hospitalized patients who started LPV/r + HCQ between 21 February and 20 March 2020. The association between the timing of treatment and the probability of 30-day mortality was assessed using univariable and multivariable logistic models. The study involved 172 patients: 43 (25%) in the ET and 129 (75%) in the DT group. The rate of clinical improvement increased over time to 73.3% on day 30, without any significant difference between the two groups (Gray's test P = .213). After adjusting for potentially relevant clinical variables, there was no significant association between the timing of the start of treatment and the probability of 30-day mortality (adjusted odds ratio [aOR] ET vs DT = 1.45, 95% confidence interval 0.50-4.19). Eight percent of the patients discontinued the treatment becausebecause of severe gastrointestinal disorders attributable to LPV/r. The timing of the start of LPV/r + HCQ treatment does not seem to affect the clinical course of hospitalized patients with COVID-19. Together with the severe adverse events attributable to LPV/r, this raises concerns about the benefit of using this combination to treat COVID-19.

Keywords: COVID-19; antiviral treatment; early; hydroxychloroquine; lopinavir; mortality.

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Conflict of interest statement

AG has received consultancy fees from Mylan and nonfinancial educational support from Gilead. GR has received grants and fees for speaker bureaux, advisory boards and CME activities from BMS, ViiV, MSD, AbbVie, Gilead, Janssen and Roche. SR has received grants, fees for speaker bureaux, advisory boards and CME activities from BMS, ViiV, MSD, AbbVie, Gilead and Janssen. CG has received grants and fees for speaker bureaux, advisory boards and CME activities from BMS, ViiV, MSD, AbbVie, Gilead, Janssen. DC has received grants and fees for speaker bureaux, advisory boards and CME activities from BMS, ViiV, MSD, Gilead, Janssen. SA has received support for research activities from Pfizer and Merck Sharp & Dome. MG has received grants and fees for speaker bureaux, advisory boards and CME activities from BMS, ViiV, MSD, AbbVie, Gilead, Janssen and Roche. GP, ALR, LO, FC, LP, LB, GC, SP, CB, VM, CC, EC and RC have nothing to declare.

Figures

Figure 1
Figure 1
Cumulative incidence of improvement (solid line) and 95%Cis (dashed lines)
Figure 2
Figure 2
Cumulative incidence of improvement in the early treatment (ET) group (dashed line) vs delayed treatment (DT) group (solid line)
Figure 3
Figure 3
Multivariable model results (adjusted odds ratios). aOR: adjusted odds ratio; CCI, Charlson Comorbidity Index; CRP, C‐reactive protein; DT, delayed treatment group; D‐d, D‐dimer; ET, early treatment group; Log, logarithmic; NA, not assigned; paO2, partial oxygen pressure
See this image and copyright information in PMC

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