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Thorax

Thorax

IF: 9
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Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings.

Published:1 March 2004 DOI: 10.1136/thorax.2003.012658 PMID: 14985565
C M Chu, V C C Cheng, I F N Hung, M M L Wong, K H Chan, K S Chan, R Y T Kao, L L M Poon, C L P Wong, Y Guan, J S M Peiris, K Y Yuen

Abstract

Background: The clinical response of patients with severe acute respiratory syndrome (SARS) to a combination of lopinavir/ritonavir and ribavirin was examined after establishing the in vitro antiviral susceptibility of the SARS associated coronavirus to a panel of antiviral agents.

Methods: The in vitro susceptibility of the prototype of SARS associated coronavirus to a panel of nucleoside analogues and protease inhibitors currently licensed for clinical use was studied. Forty one patients with SARS followed for 3 weeks were treated with a combination of lopinavir/ritonavir and ribavirin. The clinical progress and virological outcomes were monitored and compared with 111 patients treated with ribavirin only who served as historical controls.

Results: In vitro antiviral activity against SARS associated coronavirus was demonstrated for lopinavir and ribavirin at concentrations of 4 micro g/ml and 50 micro g/ml, respectively, only at 48 hours. The adverse clinical outcome (ARDS or death) was significantly lower in the treatment group than in the historical controls (2.4% v 28.8%, p<0.001) at day 21 after the onset of symptoms. The adverse outcome remained significantly lower in the treatment group than in the controls-both those diagnosed early (p<0.001) and those diagnosed later in the course of the epidemic (p = 0.002)-but there was no significant difference in adverse outcome rates between the two time periods (p = 0.548). No time related difference in outcome was observed in the control groups. A reduction in steroid usage and nosocomial infections was seen in patients initially treated with lopinavir/ritonavir, and these patients had a decreasing viral load and rising peripheral lymphocyte count. Multivariate analysis showed that age, hepatitis B carrier status, and lack of treatment with this antiviral combination were independent predictors of an adverse outcome. Lopinavir/ritonavir treatment was associated with a better outcome even when adjusted for baseline lactate dehydrogenase level.

Conclusions: The apparent favourable clinical response with lopinavir/ritonavir and ribavirin supports further randomised placebo controlled trials in patients with SARS.

Substances (3)

Related products
Procduct Name CAS Molecular Formula Supplier Price
Ribavirin 36791-04-5 C8H12N4O5 677 suppliers $5.00-$1600.00
Ritonavir 155213-67-5 C37H48N6O5S2 657 suppliers $5.00-$1290.00
Lopinavir 192725-17-0 C37H48N4O5 380 suppliers $11.72-$2590.00

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