Question: A number of drugs have recently been hyped by numerous groups, the President included. How much hope should we have for drugs like hydroxychloroquine?

Answer: Scientists are racing to try and find effective treatments for COVID-19. There are so many different potential treatments being floated, it’s hard to keep track. WHO has identified the 4 most promising drugs — a) remdisivir, b) chloroquine and hydroxychloroquine, c) ritonavir/lopinavir, d) ritonavir/lopinavir and interferon-beta — and recently launched a global trial to test them. These drugs were chosen for WHO by a panel of scientists who assessed the evidence and selected the drugs that have the highest likelihood of working, the most safety data from previous use, and are the most likely to have supplies sufficient to treat lots of people if the clinical trial(s) show they work. I’ve included below information about each of those four drugs.

In times of crisis, it’s especially important to be hopeful. But right now, we just don’t have enough solid information to know which of these drugs, if any, will work. And as with most drugs, these drugs have side effects, which means that it’s imperative to talk with your doctor before making decisions about using the drugs and/or joining a clinical trial (if that’s what you were thinking!). Finally, every clinical trial includes a data safety monitoring board that periodically reviews data on patient outcomes to assess whether the trial can continue. Simplistically — if a given treatment shows big improvements, the trial will be prematurely stopped so everyone can get the treatment. And if a given treatment shows big detriments, the trial will be prematurely stopped and folks will stop getting the treatment.

• Remdisivir is an antiretroviral drug that is taken intravenously. It is supposed to work by inhibiting viral reproduction. And it has shown promise in animal studies for treatment of other coronaviruses — MERS and SARS. It was also tested in humans as an Ebola treatment. While remdisivir did not prove to be effective for treating Ebola, it did prove to be safe for humans to use. Back in February, NIH started a drug trial of remdisivir for treatment of COVID-19. China is also conducting clinical trials of the drug and other avenues of investigation are underway. NIH’s study is scheduled to be completed today, but data from the study won’t be available until likely later this month. Chemical and Engineering News had an informative story on this topic that you might be interested in reading. In short, while scientists are hopeful, they also caution that remdisivir will likely be most effective for patients who are in early stages of the illness progression and because most patients enrolled in the trials will be at later stages of illness, the effect may be minimized.
• Chloroquine and hydroxychloroquine are old malaria drugs that are currently used to treat lupus and rheumatoid arthritis. They are taken orally. Studies have shown that these drugs can block coronaviruses (SARS) from infecting cells based on in-vitro science (e.g. lab-based science in the test tube). This article in Scientific American gives a good overview of the drugs, which are currently being tested for treating and preventing COVID-19 in clinical trials. Results from a very small, non-randomized study of 20 people treated with hydroxychloroquine daily in France showed that those who were treated had less virus in their system at treatment day 6. Anecdotal reports from China have also been positive, but to my knowledge, no scientific data supporting the claims have been published under peer review. [note: yesterday, a pre-publication (e.g. not yet peer-reviewed) was presented, which did show promising results based on a small study of 62 patients] In absence of better science, we just don’t know. Plus, both drugs do have known side-effects and risks. So, until we know whether these drugs work, and in case you were thinking about it — do NOT take them as prophylaxis! And if you are sick with COVID-19, talk with your doctor about the pros/cons of use.
• Ritonavir/lopinavir are HIV antiretroviral drugs that are taken orally. Lopinavir is a protease inhibitor that prevents viral replication and ritonavir is another type of protease inhibitor that works to enhance lopinavir. Lopinavir was shown to be effective against MERS in lab and animal tests. Initial results from a COVID-19 treatment study in China were, however, disappointing as they showed no statistically significant difference between intervention and control arms. That said, the study was underpowered (not enough people for statistically significant differences to be identified) and the direction of the differences (ex: fewer deaths in intervention arm) did show that this drug combo is likely worth exploring in large trials, which the WHO is doing. If you’re interested, this editorial in New England Medical Journal gives a good overview of the China study. Like all drugs, these drugs also have side effects. In the China study, lopinavir–ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events.
• Ritonavir/lopinavir and interferon-beta are the drugs described in the bullet above plus interferon-beta, which is a polypeptide that has immunomodulatory properties (e.g. enhances/modifies response of immune system) and is used for treatment for multiple sclerosis. This drug combination is given intravenously and has been shown to improve pulmonary function in the context of MERS. Most of what I wrote in the above bullet applies here too. Some Chinese doctors have been using a Cuban interferon drug called Alpha 2a, which they are speaking highly of, but I do not believe any data has been provided in the scientific literature yet.