Borrowing from successful malaria and HIV/AIDS prophylaxis, a new report suggests rethinking the use of a controversial Food and Drug Administration (FDA)-approved medication to avoid severe viral infection and death from COVID-19. The peer-reviewed report was published by the prestigious medical journal Infection and Drug Resistance. It is available here.
The report entitled “Flattening the Risk: Pre-Exposure Prophylaxis for COVID-19” was written by internist Raphael Stricker and nurse practitioner Melissa Fesler from Union Square Medical Associates in San Francisco, CA, and expands on a previous TrialSite News podcast. The authors have extensive experience treating patients with tick-borne diseases and recently published a proposal for early treatment of SARS-CoV-2, the viral agent of COVID-19, based on that experience.
The proposal for pre-exposure prophylaxis (PrEP) of COVID-19 focuses on hydroxychloroquine (HCQ). This controversial antimicrobial agent gained notoriety when it was considered for treatment of severe SARS-CoV-2 infection using high daily doses in combination with azithromycin. The regimen appeared to have antiviral efficacy based on reports from France and the United States, but concerns about cardiac toxicity and retinal damage have limited its use. The fact that HCQ treatment became politicized added to the controversy over its value for SARS-CoV-2 therapy.
In the latest report, the authors point out several attractive features of HCQ that were overlooked in the midst of the controversy: HCQ has an extremely long half-life of 40 days in the human body, which makes it an ideal candidate for prophylaxis of viral infection. It is approved by the FDA and has been used for malaria prophylaxis for decades in limited weekly dosing, which avoids the toxicity seen with high daily doses. It is also cheap and readily available if dosing is kept to a minimum. Other medications such as ivermectin have been suggested for disease prevention, but PrEP studies using these agents are lacking. Although feverish work on a protective COVID-19 vaccine continues, realistically a safe and effective vaccine product is nowhere in sight.
“We realized that HCQ could be safely used to avoid severe viral infection,” says Fesler. “It is the same principle that led to prevention of malaria and HIV/AIDS. We may not be able to avoid infection completely with this approach, but we hope to limit COVID-19 severity and transmission.”
The researchers pointed to groups at high risk for COVID-19, including healthcare providers and first responders, patients with hypertension, diabetes or obesity, and the elderly. Individuals who harbor Neanderthal genes also appear to be at higher risk for serious infection. Weekly PrEP with HCQ should benefit these groups and avoid severe disease. Six international cohort studies covering almost 400,000 people support this approach, and two randomized controlled trials in the United States found that 1,053 healthcare workers using HCQ PrEP had no hospitalizations, no deaths and no cardiac complications. Furthermore, once-weekly HCQ dosing appeared to work as well as twice-weekly or daily dosing. Unfortunately, the studies were terminated prematurely because of the controversy over HCQ.
“Although HCQ has been misused and demonized, it provides a sound approach to PrEP,” says Stricker. “We have an urgent need for a practical way to prevent serious viral infection, and with COVID-19 cases on the rise again and no end in sight we have everything to gain and nothing to lose with this strategy.”
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