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.,
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)
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.
Giacomelli et al., 12 Jun 2020, peer-reviewed, 20 authors.
Abstract: Received: 16 June 2020
|
Accepted: 3 August 2020
DOI: 10.1002/jmv.26407
RESEARCH ARTICLE
Early administration of lopinavir/ritonavir plus
hydroxychloroquine does not alter the clinical course
of SARS‐CoV‐2 infection: A retrospective cohort study
Andrea Giacomelli MD1,2
| Gabriele Pagani MD1,2
| Anna L. Ridolfo MD1 |
Letizia Oreni BIT2 | Federico Conti MD1,2 | Laura Pezzati MD1,2 |
Lucia Bradanini MD1,2 | Giacomo Casalini MD1,2 | Cinzia Bassoli MD1,2 |
Valentina Morena MD1,2 | Simone Passerini MD1 | Giuliano Rizzardini MD1,3 |
Chiara Cogliati MD4 | Elisa Ceriani MD4 | Riccardo Colombo MD5 |
Stefano Rusconi MD1,2
| Cristina Gervasoni MD1 | Dario Cattaneo PharmD, PhD6 |
Spinello Antinori MD1,2 | Massimo Galli MD1,2
1
Department of Infectious Diseases, ASST
Fatebenefratelli‐Sacco, Luigi Sacco University
Hospital, Milan, Italy
2
Luigi Sacco Department of Biomedical and
Clinical Sciences DIBIC, University of Milan,
Milan, Italy
3
School of Clinical Medicine, Faculty of Health
Science, University of the Witwatersrand,
Johannesburg, South Africa
4
Department of Internal Medicine, ASST
Fatebenefratelli‐Sacco, Luigi Sacco Hospital,
Milan, Italy
5
Department of Anesthesiology and Intensive
Care, ASST Fatebenefratelli‐Sacco, Luigi Sacco
Hospital, Milan, Italy
6
Unit of Clinical Pharmacology, ASST
Fatebenefratelli‐Sacco, Luigi Sacco University
Hospital, Milan, Italy
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
Correspondence
Andrea Giacomelli, MD, Luigi Sacco
Department of Biomedical and Clinical
Sciences DIBIC, University of Milan, III
Infectious Diseases Unit, L. Sacco Hospital,
Via G.B. Grassi 74, 20157 Milano, Italy.
Email: andrea.giacomelli@unimi.it
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
antiviral treatment, COVID‐19, early, hydroxychloroquine, lopinavir, mortality
Andrea Giacomelli, Gabriele Pagani, and Anna L. Ridolfo contributed equally to the study.
J Med Virol...
Late treatment
is less effective
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