Lack of viral clearance by the combination of hydroxychloroquine and azithromycin or lopinavir and ritonavir in SARS-CoV-2-related acute respiratory distress syndrome
Hraiech et al.
, Lack of viral clearance by the combination of hydroxychloroquine and azithromycin or lopinavir and ritonavir..
, Ann. Intensive Care, doi:10.1186/s13613-020-00678-4
Retrospective 45 ICU patients, 17 treated with HCQ+AZ, showing no significant difference in viral clearance after 6 days, or mortality 6 days from ARDS.
This study is excluded in the after exclusion results of meta
very late stage, ICU patients.
risk of death, 64.7% lower, RR 0.35, p = 0.21, treatment 2 of 17 (11.8%), control 5 of 15 (33.3%), NNT 4.6, day 38 +- 7.
risk of death, 376.5% higher, RR 4.76, p = 0.49, treatment 2 of 17 (11.8%), control 0 of 15 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm), day 6 from ARDS.
risk of no viral clearance, 2.9% higher, RR 1.03, p = 1.00, treatment 14 of 17 (82.4%), control 8 of 10 (80.0%), day 6 from treatment.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Hraiech et al., 24 May 2020, retrospective, France, peer-reviewed, 8 authors, average treatment delay 7.0 days.
Abstract: (2020) 10:63
Hraiech et al. Ann. Intensive Care
LETTER TO THE EDITOR
Lack of viral clearance by the combination
of hydroxychloroquine and azithromycin
or lopinavir and ritonavir in SARS‑CoV‑2‑related
acute respiratory distress syndrome
Sami Hraiech1,2* , Jérémy Bourenne2,3, Khaldoun Kuteifan4, Julie Helms5, Julien Carvelli2,3, Marc Gainnier2,3,
Ferhat Meziani5 and Laurent Papazian1,2
The current international outbreak of respiratory illness
due to SARS-CoV-2 and named Covid-19 can evolve to
severe progressive pneumonia and acute respiratory distress syndrome (ARDS), multiorgan failure, and death.
Up to now, there are no specific therapeutic agents for
coronavirus infections. Lopinavir–ritonavir treatment
recently failed to demonstrate any significant outcome
benefit, but the study was underpowered to rule out
clinically meaningful treatment effects, and the intervention was started a median of 13 days after symptoms
onset . In vitro inhibition of virus spread has been
reported with chloroquine prior to or after SARS-CoV-2
infection . Hydroxychloroquine has been found to be
more potent than chloroquine to inhibit SARS-CoV-2
in vitro  and a recent report suggested that 70% of
20 non-ICU hydroxychloroquine-treated patients had
negative PCR results in nasopharyngeal samples at day
6 (D6) post-inclusion  and in all the 6 patients treated
with hydroxychloroquine and azithromycin combination
(hydroxychloroquine–azithromycin) . In order to evaluate these results in intensive care unit (ICU) patients,
we retrospectively assessed in moderate-to-severe ARDS
the efficacy of hydroxychloroquine–azithromycin combination regarding viral disappearance at both day 6 of the
treatment and day 6 of evolution of ARDS as compared
Assistance Publique ‑ Hôpitaux de Marseille, Hôpital Nord, Médecine
Intensive Réanimation, Hôpital Nord, 13015 Marseille, France
Full list of author information is available at the end of the article
with patients treated with lopinavir–ritonavir and a control group without any anti-viral treatment.
Forty-five patients were included, 17 receiving the
combination of hydroxychloroquine 600 mg and azithromycin 500 then 250 mg daily, 13 receiving lopinavir–
ritonavir 800 mg daily and 15 who did not receive any
anti-viral treatment (controls). Patients were admitted
to 4 ICUs in 2 different regions of France from March
2nd to March 31st. In one ICU, they received hydroxychloroquine–azithromycin as a usual policy while this
combination was maintained if started prior to admission in the second ICU (the other patients receiving lopinavir–ritonavir). Controls were treated in 2 other ICUs
with antibiotics targeting bacterial community acquired
pneumonia only. In all patients, nasopharyngeal PCR for
SARS-CoV-2 were performed at the time of diagnosis
and then regularly during ICU stay in order to assess viral
clearance. Results of PCR were qualitative at the beginning of the pandemic, then quantitative and expressed by
the PCR cycle threshold (CT).
Data were expressed as mean ± the standard deviation or median with interquartile range for the quantitative variables, and as numbers and percentages for the
categorical variables. Groups were compared using the
Chi-square or Fisher’s exact test for categorical characteristics, and using the Student’s t test or Mann–Whitney
U test for continuous ones. A two-sided p value of less
is less effective
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