Remdesivir and COVID-19.

The Panel on Antiretroviral Guidelines for Adults and Adolescents with HIV and the American Association for the Study of Liver Diseases guidelines for hepatitis C virus treatment suggest that combination therapy for severe acute respiratory syndrome coronavirus 2 infection will outperform single drugs. Yeming Wang and colleagues reported that the hazard of 28-day clinical improvement for 158 patients with severe COVID-19 randomly assigned to remdesivir was 1·2 times (95% CI 0·9 to 1·8) the hazard of patients randomly assigned to placebo, but the 28-day mortality in both these groups was similar. Relatedly, Cao and colleagues reported that the hazard of 28-day clinical improvement for 99 patients with severe COVID-19 randomly assigned to lopinavir-ritonavir was 1·3 times (95% CI 1·0 to 1·8) the hazard among 100 patients randomly assigned to standard care, and the 28-day mortality was reduced by 6% (95% CI −17 to 6). Nearly 20% of patients in the Wang and colleagues trial were also receiving lopinavir-ritonavir, but their results are not stratified by lopinavir-ritonavir status. Reporting estimates stratified by concomitant lopinavir-ritonavir use would help guide the design of future (factorial) trials that investigate the joint effects of these two therapies, even if imprecise. Also, reporting the proportion of patients clinically improved at 28 days is more interpretable than the hazard ratio.

Additionally, Wang and colleagues report that the effect of remdesivir on clinical improvement appeared stronger among patients who started treatment within 10 days of symptom onset than among those who started later. Cao and colleagues reported similar strengthening of the lopinavir-ritonavir treatment effect among patients who started treatment within 14 days of symptom onset. As in HIV, timing of treatment initiation for COVID-19 appears to be of crucial importance in the design of future research.