Treatment of severe acute respiratory syndrome with lopinavir/ritonavir: a multicentre retrospective matched cohort study

KS Chan, ST Lai, CM Chu, E Tsui, CY Tam, MML Wong, MW Tse, TL Que, JSM Peiris, J Sung, VCW Wong, KY Yuen
Department of Medicine and Geriatrics, United Christian Hospital, 130 Hip Wo Street, Kwun Tong, Hong Kong

OBJECTIVES. To investigate the possible benefits and adverse effects of the addition of lopinavir/ritonavir to a standard treatment protocol for the treatment of severe acute respiratory syndrome.

DESIGN. Retrospective matched cohort study. SETTING. Four acute regional hospitals in Hong Kong.

PATIENTS AND METHODS. Seventy-five patients with severe acute respiratory syndrome treated with lopinavir/ritonavir in addition to a standard treatment protocol adopted by the Hospital Authority were matched with controls retrieved from the Hospital Authority severe acute respiratory syndrome central database. Matching was done with respect to age, sex, the presence of co-morbidities, lactate dehydrogenase level and the use of pulse steroid therapy. The 75 patients treated with lopinavir/ritonavir were divided into two subgroups for analysis: lopinavir/ritonavir as initial treatment, and lopinavir/ritonavir as rescue therapy. These groups were compared with matched cohorts of 634 and 343 patients, respectively. Outcomes including overall death rate, oxygen desaturation, intubation rate, and use of pulse methylprednisolone were reviewed.

RESULTS. The addition of lopinavir/ritonavir as initial treatment was associated with a reduction in the overall death rate (2.3%) and intubation rate (0%), when compared with a matched cohort who received standard treatment (15.6% and 11.0% respectively, P<0.05) and a lower rate of use of methylprednisolone at a lower mean dose. The subgroup who had received lopinavir/ritonavir as rescue therapy, showed no difference in overall death rate and rates of oxygen desaturation and intubation compared with the matched cohort, and received a higher mean dose of methylprednisolone.

CONCLUSION. The addition of lopinavir/ritonavir to a standard treatment protocol as an initial treatment for severe acute respiratory syndrome appeared to be associated with improved clinical outcome. A randomised double-blind placebocontrolled trial is recommended during future epidemics to further evaluate this treatment.

Hong Kong Med J 2003;9:399-406

Key words: Coronavirus; Protease inhibitors; SARS virus; Treatment outcome