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No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection

Molina et al., Médecine et Maladies Infectieuses, 50:4, doi:10.1016/j.medmal.2020.03.006 (date from preprint)
Mar 2020  
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HCQ for COVID-19
1st treatment shown to reduce risk in March 2020
*, now with p < 0.00000000001 from 411 studies, recognized in 46 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,300+ studies for 75 treatments.
Report on 11 patients treated with HCQ with no control group. Authors suggest there is no evidence of benefit for HCQ based on PCR+ results for 8/10 patients at day 5-6. Binary PCR evaluation with an unknown Ct. Binary PCR does not distinguish replication-competence.
Molina et al., 28 Mar 2020, peer-reviewed, 7 authors.
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Abstract: See discussions, stats, and author profiles for this publication at: No Evidence of Rapid Antiviral Clearance or Clinical Benefit with the Combination of Hydroxychloroquine and Azithromycin in Patients with Severe COVID-19 Infection Article in Médecine et Maladies Infectieuses · March 2020 DOI: 10.1016/j.medmal.2020.03.006 CITATIONS READS 341 1,047 7 authors, including: Constance Delaugerre Breno Melo-Lima Assistance Publique – Hôpitaux de Paris Paris Diderot University-INSERM 172 PUBLICATIONS 4,647 CITATIONS 8 PUBLICATIONS 361 CITATIONS SEE PROFILE SEE PROFILE Lauriane Goldwirt Nathalie De Castro Hôpital Saint-Louis (Hôpitaux Universitaires Saint-Louis, Laboisière, Fernand-Widal) Hôpital Saint-Louis (Hôpitaux Universitaires Saint-Louis, Laboisière, Fernand-Widal) 63 PUBLICATIONS 962 CITATIONS 82 PUBLICATIONS 1,789 CITATIONS SEE PROFILE Some of the authors of this publication are also working on these related projects: ANRS 138 EASIER trial View project ANRS-PREVENIR View project All content following this page was uploaded by Breno Melo-Lima on 15 April 2020. The user has requested enhancement of the SEE PROFILE G Model MEDMAL-4279; No. of Pages 2 ARTICLE IN PRESS Médecine et maladies infectieuses xxx (2020) xxx–xxx Disponible en ligne sur ScienceDirect Letter to the editor No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection The COVID-19 epidemic is the worst worldwide pandemic in a century with more than 500,000 cases and 25,000 deaths so far. In France, more than 30,000 cases have been reported up to March 27, and nearly 2000 have died. Pending the availability of a vaccine, there is a critical need to identify effective treatments and a number of clinical trials have been implemented worldwide. Chloroquine analogs have been shown to inhibit the acidification of endosomes and to exhibit in vitro a non-specific antiviral activity at high micromolar concentration against a broad range of emerging virus (HIV, dengue, hepatitis C, chikungunya, influenza, Ebola, SARS and MERS viruses) and more recently COVID-19 [1,2]. In France, following the results of a clinical study in Marseille, there is considerable interest for the use of hydroxychloroquine to treat COVID-19 disease, and the French Ministry of Health recently allowed the use of hydroxychloroquine to treat COVID-19 disease pending the results of ongoing clinical trials [3]. In their study, Gautret et al. reported a 100% viral clearance in nasopharyngeal swabs in 6 patients after 5 and 6 days of the combination of hydroxychloroquine and azithromycin [3]. This rate of viral clearance was lower with hydroxychloroquine alone (57.1%) and was only 12.5% in patients who did not receive hydroxychloroquine (P < 0.001). Such a rapid and full viral clearance was quite unexpected and we wished to assess in a prospective study virologic and clinical outcomes of 11 consecutive patients hospitalised in our department who received hydroxychloroquine (600 mg/d for 10 days) and azithromycin (500 mg day 1 and 250 mg days 2 to 5) using the same dosing regimen reported by Gautret et al. [3]. There were 7 men and 4 women with a mean age of 58.7 years (range: 20–77), 8 had significant comorbidities associated with poor outcomes (obesity: 2; solid cancer: 3; hematological cancer: 2;..
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Late treatment
is less effective
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