Major countries around the world have been running analyses of existing drugs, some are antivirals in their own right and others are would be re-purposed. Drugs like Remdesivir and Kaletra. Remdesivir was originally developed for Ebola but existing information (including preliminary use data) suggests it may be active against COVID-19. Kaletra is a combination of three antiretrovirals used for the treatment of HIV.
One of the key variables in the treatment of most any viral disease is when to intervene with novel agents in the face of a patient’s clinical deterioration. As a result, we treat the sickest patients first which may not be the best strategy. For example, with the first drugs for HIV the initial studies were in people with AIDS and an anticipated life expectancy of only nine months. Later the drugs were demonstrated to work best when administered to patients early in the course of the disease.
For most antiviral drugs, including drugs for herpes, HIV, influenza, respiratory syncytial virus are best if administered early in the course of the illness. This paradigm is currently being used to evaluate potential drugs for COVID-19; we are starting with the sickest patients first — primarily those who are intubated. I suspect this is wrong.
A recent paper in the New England Journal of Medicine essentially closed the door to hydroxychloroquine, demonstrating that is was no better than no treatment. But again, while I am not advocating hydroxychloroquine, (I suspect it is indeed inert against COVID-19) it was tested in practice to the sickest patients (e.g. patients intubated or in respiratory failure; patients with less than a 50% chance of recovering). The question remains, “Did we study the drug in the right stage of disease to emphasize a treatment effect”. While this question is no longer important for hydroxychloroquine (as it had no scientific basis for activity) it is critical that emerging antivirals including Remdesivir, Kaletra, and the tens of drugs waiting to be tested, be evaluated in the correct population and historically this means people shortly after the presentation of symptoms.
Dr. John Andrews, “Doc John” of Lead, has a doctorate in virology, immunology, and microbiology who, after a career in developing prescription drugs, is now working on drug development to target COVID-19. He will be offering columns every two weeks about the progress of finding a vaccine for the virus.
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