Editor's note: On April 29, early results from two noteworthy studies on remdesivir were released. One small study from China showed remdesivir had no benefit for people with COVID-19. Findings from a larger study conducted by the NIH showed remdesivir reduced recovery time by 4 days and lowered mortality rates. Read our follow-up story on these findings.
Our original article, published on April 2, continues below.
Amid the current coronavirus crisis, HIV antiretrovirals have been getting far more mainstream attention than they usually do. First, it was thought that the longtime (and outdated) HIV medication lopinavir/ritonavir (Kaltera) might have some activity against COVID-19, which is actually the name of the illness, with SARS-CoV-2 being the actual name of the virus. (Much as HIV is the name of the virus, and “AIDS,” or now “HIV disease,” is the name of the illness.)
But then lopinavir/ritonavir failed against COVID-19 in a decently sized study in China. While there are still other trials planned to investigate this medication, many lost hope in its promise after news of this study broke.
Now everyone is waiting on several studies to see if the investigational HIV drug remdesivir, in the same broad family as a handful of longtime HIV drugs including lamivudine (3TC, Epivir) and emtricitabine (FTC, Emtriva), has activity against COVID-19. (A few years ago, the agent killed SARS and MERS, two similar coronaviruses, in lab dishes.) We may see those results in early April.
Demand for remdesivir has spiked so high, especially after President Trump name-checked it as a promising agent at a March 19 press conference, that the drug's developer Gilead has pulled back from offering it prior to its U.S. Food and Drug Administration approval under the urgent-need caveat called “compassionate use.”
It all raises the question of why we think HIV drugs would work against COVID-19—or, more broadly, why we think drugs that work against one virus would work against any other.
One part of the answer is that there’s a precedent: It’s been known for years that the very similar antiretrovirals 3TC and FTC also work against hepatitis B. (FTC is a component of two fixed-dose combination drugs, sold under the brand names Truvada and Descovy, that are also used for HIV pre-exposure prophylaxis [PrEP].) Even though HIV and hep B are very different-looking viruses, 3TC and FTC disable the self-replication process that both viruses undertake once in the body.
“They both block the [replication] instructions,” says Mark Harrington, executive director of the pioneering HIV research and advocacy nonprofit Treatment Action Group.
But that’s a rare instance of a drug having activity across viruses.
“There are so many other factors, such as what kinds of human cells viruses live inside and what kinds of host and viral proteins they require to replicate,” says Harrington, referring to the parts of viruses that bond to human cells and then get inside them to do their self-replication work. “We have antibiotics that work against different kinds of bacteria, broad-spectrum antibiotics, because bacteria have a lot of similar enzymes and proteins.”
To find a broad-spectrum drug that worked against several viruses, says Harrington, “would be the holy grail.” But he says that won’t be easy. “They’re even having trouble creating a vaccine that would treat all forms of flu, because flu mutates so quickly.” (It has been learned, however, that the COVID-19 virus seems to mutate slowly, which is good news in terms of developing a vaccine that could be used for more than one season.)
“A broad-spectrum antiviral drug would be really hard to do,” he says, “because each virus has a different suite of proteins—and the mechanics of replication look different in each virus. The fact that the HIV drugs 3TC and FTC work against both hep B and HIV is very unusual in the world of antivirals.”
Thankfully, most people’s immune systems are strong enough to fight off viruses like flu and coronavirus. That’s why, absent large and well-structured trials that test a large cohort of patients’ coronavirus viral load both before and after treatment, it’s hard to know at this point if those with COVID-19 who took an antiviral—such as the investigational remdesivir—and then got better were aided by the drug specifically, or whether their own immune system also played a role.
“The most effective approach to treating this disease is our own immune system, which frankly is quite a miracle,” says Tim Flanigan, M.D., an infectious diseases specialist at Brown University who is currently treating COVID-19 cases throughout Rhode Island. “That’s why I’m quite confident that HIV patients on HIV treatment with high CD4 counts will be able to” fight off COVID-19.
In recent weeks, several HIV clinicians nationwide have echoed this, bringing a measure of relief to thousands of worried HIV-positive people.
But Harrington also stresses that the stage has been well set to move quickly on research into which new or existing drugs of any sort could work against COVID-19. Indeed, in late March, a team of researchers announced that they had identified 69 such compounds, and that two dozen of them were already being studied.
“We’re lucky enough to have had the biomedical research enterprise over the last 20 years looking at new and emerging pathogens such as the original SARS, MERS, and H1N1,” Harrington says. “So we have 20 years of data of this family of emerging viruses, which is why we’re able to move rapidly with studies of drugs like remdesivir.”
Current studies of remdesivir against COVID-19 are looking at patients with both moderate and severe forms of the illness, to determine if the drug can reduce not only its duration but its severity. The studies should assess rates of hospitalization prevention, says Harrington.
The trouble, he says, is when public figures tout agents prematurely, before proper studies to determine efficacy. President Trump has done this in recent days, not only with remdesivir but with the common anti-malaria drug chloroquine—which he claimed, in a tweet, could work in tandem with the antibiotic azithromycin (the “Z-Pack”) to be “one of the biggest game changers in the history of medicine.”
“In any sane world,” says Harrington, “you wouldn’t have the President out there making these recommendations. What he should be saying is that the FDA is working with academic scientists and companies worldwide to quickly identify candidates to study in drug and vaccine trials, and that Congress should give them more money for that research. He should not be singling out drugs that he heard about on Fox [News].”
Of National Institutes of Health honcho Anthony Fauci, M.D., with whom Harrington negotiated decades ago to retool the HIV drug-development process, and who now almost daily must find ways of politely correcting Trump’s medical misinformation during press conferences, Harrington says: “He’s in a tough position, because he has to speak truth to power—and this president doesn’t care about the truth.”
“But,” he added, “we need Fauci to push to make sure that trials for these potential COVID-19 drugs move forward rapidly. I think they’re moving as fast as they can on that front.”