The Myth that HCQ Interferes with RDV

It is increasingly clear that on June 15, the FDA executed two coordinated attacks against Hydroxychloroquine (HCQ). One was the EUA revocation, supported by a junk science memo, and a press release saying “the FDA determined that chloroquine and hydroxychloroquine are unlikely to be effective in treating COVID-19 for the authorized uses in the EUA(emphasis is added). The Big Tech and MSM distorted this already incorrect determination by omitting the last clause.

But within hours of this press release, the FDA issued another attack with a scary title Coronavirus (COVID-19) Update: FDA Warns of Newly Discovered Potential Drug Interaction That May Reduce Effectiveness of a COVID-19 Treatment Authorized for Emergency Use. This “update”  started with

“Today, the U.S. Food and Drug Administration is warning health care providers about a newly discovered potential drug interaction related to the investigational antiviral drug remdesivir, which has received emergency use authorization for the treatment of hospitalized COVID-19 patients with severe disease.

Based on a recently completed non-clinical laboratory study, the FDA is revising the fact sheet for health care providers that accompanies the drug to state that co-administration of remdesivir and chloroquine phosphate or hydroxychloroquine sulfate is not recommended as it may result in reduced antiviral activity of remdesivir.”

These carefully crafted sentences insinuate several falsehoods. The facts are:

  • Remdesivir (RDV) has no or very low antiviral activity against the Wuhan coronavirus
  • HCQ was co-administered with RDV in clinical trials, and led to lower mortality (9% in the HCQ+RDV patients vs 12% in the RDV patients; [1] Appendix, Table S3. Baseline Predictors of Time to Clinical Improvement)
  • Laboratory studies have very low value when real clinical data is available
  • The mentioned non-clinical laboratory study was performed with chloroquine phosphate, not hydroxychloroquine sulfate. Reportedly, chloroquine phosphate caused decreased production of Remdesivir triphosphate in-vitro. This is not relevant to hydroxychloroquine sulfate.

In hindsight, this warning was intended as another signal to doctors, hospitals, public health bureaucrats, instructing them not to treat patients with Hydroxychloroquine. HCQ does not interfere with RDV, but with the revenues of its manufacturer Gilead. The FDA officials and Gilead colluded to prevent the use of HCQ for COVID-19 in order to sell RDV.

Here is how this narrative played out in Arkansas, (from Arkansas lawmakers debate over use of hydroxychloroquine for coronavirus, KATV, August 31):

[Arkansas Health Secretary] Dr. Romero said remdesivir is more effective, and can have negative effects in combination with hydroxychloroquine. “We now can use remdesivir in all hospitalized patients,” he said. “That’s how strongly the FDA feels it can work.”

Of course, Remdesivir (RDV) is not more effective than HCQ. Even Gilead claims that RDV shortens hospital stay by a few days, something which is hard to notice or to argue against. Also notice how far the “HCQ is bad, RDV is good” narrative was successfully promoted  due to the deplatforming of the opposition. For example, the FDA has never claimed that Remdesivir can have negative effects in combination with hydroxychloroquine.

There were also some psychological tricks used. A supply shortage  of RDV created the impression that it is in high demand. Also, RDV is 200x more expensive than HCQ, so it might be perceived as more effective.

The KATV article mentions that State Senator Jason Rapert (R) was hospitalized with COVID-19 in July. He asked to be treated with hydroxychloroquine. The hospital denied his request and treated him with RDV. Similar situations have happened in many other states. In the first half of August, RDV was prescribed at ~75% rate of HCQ, according to my recent survey (See COVID-19 Treatment Aug ii Super.xlsx within the Attachment Zip). If HCQ would be used properly (i.e., given to most patients over 40 early on symptoms with Azithromycin and Zinc), there would be no need for RDV. Barr’s DOJ should get involved.

Arkansas is marked in Red on the map of America’s Frontline Doctors’ Summit  as a state where it is nearly impossible to legally obtain Hydroxychloroquine.

By the way, 27% (109/397) of the patients in this RDV trial, conducted by Gilead, also received HCQ [1]. It is not reported, but the past experience teaches that patients who received HCQ were likely sicker than those who did not. They still had lower mortality. The paper mentions the concomitant use of Azithromycin, although does not give the numbers. Somebody needs to ask for the raw data, and to re-analyze it as HCQ vs HCQ+AZ vs placebo trial.

Technical Details

From the Remdesivir Fact Sheet, updated on June 15:

Coadministration of remdesivir and chloroquine phosphate or hydroxychloroquine sulfate is not recommended based on in vitro data demonstrating an antagonistic effect of chloroquine on the intracellular metabolic activation and antiviral activity of remdesivir …

The EC50 values of remdesivir against SARS-CoV-2 in Vero cells was 137 nM at 24 hours and 750 nM at 48 hours post-treatment. The antiviral activity of remdesivir was antagonized by chloroquine phosphate in a dose-dependent manner when the two drugs were co-incubated at clinically relevant concentrations in HEp-2 cells infected with respiratory syncytial virus (RSV). Higher remdesivir EC50 values were observed with increasing concentrations of chloroquine phosphate. Increasing concentrations of chloroquine phosphate reduced formation of remdesivir triphosphate in normal human bronchial epithelial cells.

Thus, Gilead reported two in-vitro tests:

  • One tested Remdesivir with chloroquine phosphate against a virus unrelated to coronaviruses
  • The second tested production of remdesivir triphosphate in the presence of chloroquine phosphate, and found that less of it is produced

These tests involved neither hydroxychloroquine nor any coronavirus, but the FDA and Gilead used them to discourage the use of HCQ.

On July 10, Gilead issued a press release, which falsely claimed that “the rates and likelihood of recovery were lower in patients who received concomitant hydroxychloroquine compared with patients treated with remdesivir who did not receive hydroxychloroquine.”

In the past, the media used to be critical and suspicious in such situations – when a huge drug company tests its own ultra-expensive drug against readily available and inexpensive competitors. But Gilead is a Silicon Valley company, so its fellow Big Tech and the fake news media gave Gilead a pass.

[1]        Goldman JD, Lye DCB, Hui DS, Marks KM, Bruno R, Montejano R, et al. Remdesivir for 5 or 10 Days in Patients with Severe Covid-19. N Engl J Med 2020.

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