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

Giacomelli et al., Journal of Medical Virology, doi:10.1002/jmv.26407 (date from earlier preprint)

Giacomelli et al., Early administration of lopinavir/ritonavir plus hydroxychloroquine does not alter the clinical course of.., Journal of Medical Virology, doi:10.1002/jmv.26407 (date from earlier preprint)

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Late stage study of hospitalized patients comparing treatment starting within 5 days versus later. Note that "early" here is only relative - all patients are hospitalized so this is "late" and "very late". The "early" treatment group is significantly older. Severe adverse events attributed by authors to concurrent administration of LPV, making it difficult to make conclusions about HCQ.

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Giacomelli et al., 12 Jun 2020, peer-reviewed, 20 authors.

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

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

Journal of Medical Virology, doi:10.1002/jmv.26407

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.

AUTHOR CONTRIBUTIONS AG and GP designed the study. LO, AG, and GP were responsible for the statistical analysis. All authors contributed in the patient's enrolment, data collection and interpretation. AG and GP had contributed to the preliminary draft of the manuscript. ALR and MG critically revised the manuscript. All authors approved the final version of the manuscript.

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Late treatment
is less effective

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