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

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

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.

MeSH terms

  • Aged
  • Antiviral Agents / therapeutic use*
  • COVID-19 Drug Treatment*
  • Drug Combinations
  • Female
  • Humans
  • Hydroxychloroquine / therapeutic use*
  • Italy
  • Lopinavir / therapeutic use*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Ritonavir / therapeutic use*
  • SARS-CoV-2 / drug effects*

Substances

  • Antiviral Agents
  • Drug Combinations
  • Lopinavir
  • Hydroxychloroquine
  • Ritonavir