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

BACKGROUND: 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. METHODS: To compare the rate of clinical improvement between those who started LPV/ritonavir (LPV/r)+HCQ within five 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 uni- and multivariable logistic models. RESULTS: 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=0.213). 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 because of severe gastrointestinal disorders attributable to LPV/r. CONCLUSION: The timing of the start of LPV/r+HCQ treatment does not seem to affect the clinical course of hospitalised 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. This article is protected by copyright. All rights reserved.