Lundquist Institute HIV/AIDS researcher refocuses on COVID-19, in search of treatment
Dr. Eric Daar outside The Lundquist Institute, where he and colleagues are conducting clinical trials in search of a COVID-19 treatment. Photo by David Fairchild (DavidFairchildStudio.com)
The Lundquist Institute researchers lead race to slow COVID-19 hospitalizations
Dr. Eric Daar has researched HIV and AIDS for nearly three decades. Daar is Chief of HIV Medicine at the Harbor UCLA Medical Center, a researcher at The Lundquist Institute (formerly LA BioMed) and a professor at UCLA’s Geffen School of Medicine.
On March 21, two days after California Governor Gavin Newsom issued his Stay At Home order, Daar’s focus on HIV and AIDS changed to COVID-19.
“That day,” the Rancho Palos Verdes resident said, “I received an email from the National Institute of Health. NIH needed people with expertise in conducting large clinical trials and it needed research sites to deploy those trials.”
Daar is a member of a long established AIDS clinical trial group.
“NIH wanted to enlist our group because the country didn’t have a lot of researchers looking at coronaviruses until the pandemic. So those of us who had a long experience with other viral diseases were asked to take on this new challenge.
“During a pandemic, it’s all about using existing resources and expertise to roll out treatment in as short an order as possible,” Daar explained.
“The first thing people do is look at what drugs are on the shelf, because those are drugs that we can move forward with almost immediately.
“The second step is to design new drugs specific to that pathogen. But new drugs take time because you’re starting from scratch. Once you have a molecule that looks promising in the lab, you have to test it in animals. Then you have to test it in a small number of humans. You have to test the pharmacology [side effects]. Then you have middle sized studies. All this can take years.
“That’s the reason we look at what’s on the shelf. Because there is an urgency. People are dying,” he said.
“An example of an off the shelf drug that shows promise of being effective against COVID-19 is Remdesivir. It had been tested without success against Ebola (which is not a coronavirus). But it met the criteria of a drug that, in the test tube, looked to be active against this virus and had already been used in humans. So we knew the pharmacology, we knew how to dose it.
“But Remdesivir is not practical, except for hospital patients, because it’s administered intravenously. We’re not going to take people in an outpatient setting and infuse them with the drug every day.
“Another drug that was on the shelf was a drug we used for HIV for years. That’s still being studied.
“The drugs our group have been asked to study are hydroxychloroquine, taken in combination with azithromycin,” Daar said.
“This is the combination President Trump has been talking about. But I’m pretty sure, based on what he’s been saying, that he’s just taking hydroxychloroquine. And just for prevention.”
“Hydroxychloroquine is available for people with lupus, rheumatoid arthritis, and malaria. So we knew we could put it into humans and it is available.
“Its relevance to COVID-19 is that it is able to block the entry of microorganisms into that part of cells where the virus reproduces,” Daar said. “Azithromycin is a broad-spectrum antibiotic, commonly sold as Z-pak. It may be useful to prevent bacterial complications arising from the viral infection,” he said.
Trump’s advocacy of the two drugs and the media’s response created potential complications for the trial, Daar acknowledged.
“There’s a lot of craziness going around about these two drugs.
“When we started putting together the protocol for the study about six weeks ago, there were concerns that people wouldn’t enroll in a placebo-controlled study because everybody was already convinced hydroxychloroquine worked. Then new studies came out that it didn’t work and we were concerned people wouldn’t enroll for the opposite reason.
“But we have no good data, whatsoever, arguing for or against the role of hydroxychloroquine, alone or with azithromycin, for prevention or treatment. There were early studies that were promising, but they were extremely limited. And there were later studies that suggested hydroxychloroquine didn’t work. And they were extremely limited.”
The NIH study will involve over 2,000 patients, at over two dozen clinical labs. The patients will be over 60 and in the early stages of COVID-19 and not in need of hospitalization. Approximately 20 percent of COVID-19 patients require hospitalization.
“Can we reduce that 20 percent to 15 percent and prevent that five percent from possibly dying? That’s the first question we want to answer. It’s a well designed study that has the chance to definitively answer that question, which none of the other studies so far have been able to do.”
A second goal is to determine if the drug combination reduces symptoms and hastens recovery.
A third goal will involve a subset equaling 10 percent of the enrollees who will be given blood tests and nose swabs to measure their viral “load.”
“We don’t know if we need large clinical studies to look for real hard endpoints [successes], like reduced admissions to the hospital and fewer deaths.
“In those 10 percent of enrollees, we’re going to look at the amount of virus from their nose when we first meet them. And again a week after therapy, and again three weeks after therapy to see if the amount of virus goes away more quickly among those taking the medication than it does among those taking the placebo.
“It’d be nice, if rather than having to enroll 2,000 people and follow them for four weeks, we could enroll say 50 people and just look at what happens to the virus in their noses and know if the trial drug makes the virus go down, that the outcomes will be better.
“It’s not an efficient way to test new drugs, to always have to enroll 2000 people. What we’d love to do is develop a so-called surrogate marker. In the world of HIV, we validate whether drugs work by looking at the amount of virus in the patient’s blood. We can do that in a matter of weeks, but only because we were able to demonstrate, many years ago, that a change in virus in the blood translated into clinical improvements.”
The decision to test hydroxychloroquine in combination with azithromycin was based on expediency, Daar said.
“We realize if this works, we won’t know for sure if you need to administer them in combination or not. But if we did a study with just the hydroxychloroquine and it didn’t work, we would have never known whether the combination would work. Or, if we tried to do a study that included one trial with hydroxychloroquine, a second trial with hydroxychloroquine and azithromycin and a third trial with only a placebo, then we’d be looking at a study that might take years.
Daar said protocols for clinicals studies of this scale typically take four to six months to prepare. Because of the urgency, he and his team developed the protocols for studying 2,000 people at two dozen sites around the country in just four weeks. The three local sites are The Lundquist Institute, UCLA Medical Center and Los Angeles County USC.
Daar and fellow researchers began interviewing patients for the trial last week. Enrollees in the clinical trial must present a medical report as evidence they have COVID-19.
“We meet them in the parking lot, give them instructions, give them a packet with pills for seven days and send them home,” he said.
Researchers call the enrollees daily to remind them to take their pills and to record their symptoms in a journal.
The researchers, including Daar, do not know which enrollees receive hydroxychloroquine and azithromycin and which receive placebos.
COVID-19 stats
“People are overly optimistic when talking about developing vaccines in record times. We’ve never developed a vaccine for a coronavirus,” Daar pointed out.
“The SARS virus (Severe Acute Respiratory Syndrome, in 2002) and the MERS virus (Middle East Respiratory Syndrome, in 2012) weren’t around long enough for vaccines or even treatments to be developed. Fortunately, they didn’t transmit very efficiently, so the number of cases were small.”
In the U.S. 1.72 million have contracted COVID-19 and nearly 100,000 have died, a mortality rate of about 6 percent.
In California 90,631 have contracted COVID-19 and 3,708 have died, a mortality rate of about 4 percent.
Just 8,000 people worldwide contracted the SARS virus, the majority of them in China. The MERS virus infected fewer than 2,500 people, 80 percent of them in Saudi Arabia. SARS had a 10 percent mortality rate and MERS a 37 percent mortality rate.
“Even if we’re fortunate enough to find a safe, effective vaccine, we don’t know it’ll be 100 percent effective. We have a flu vaccine that comes out every year. But it is never 100 percent effective. So we may need both the vaccine and treatment to minimize the morbidity rate.”
The Center for Disease control estimates that between October 2019 and April 2020, 39 million to 56 million people in the U.S caught the flu and 24,000 to 62,000 died as a result, or less than one percent.
“There are new designer drugs being developed to target coronavirus. My colleagues and I are already in the process of developing protocols to start those studies,” Daar said.
Moving forward
“I’m not sure my guess is any better than anyone else’s about the future of coronavirus. But we’ve been very fortunate in California and Los Angeles in that we’ve been able to tamp it down by closing things down early. There’s no doubt everybody’s ready to start to open things up, which I think is reasonable. If it’s done slowly, with a lot of caution.
“We will know in a few weeks to a month what the impact of starting to open things up will have on the spread of the virus. It’ll depend a lot on how careful people are about social distancing. Wearing masks will continue to be important, especially in settings where you can’t maintain six feet apart. If we can do that, I think we can keep the curve relatively flat.
“One of the problems at the beginning, why things were going out of control, is we had no way of measuring the number of cases. Now we’re doing much more testing, maybe not quite enough, but much more.
“If we’re able to maintain where we are, the next big question will be whether we’ll see a resurgence of the disease in the fall, like we do with many respiratory infections, including influenza.”
In a 2012 Peninsula magazine interview, Daar traced his interest in HIV/AIDS research to being at Georgetown Medical School in the early 1980s, when the disease emerged.
“Then it really began to explode in the years of my residency,” he said.
“It was interesting to be involved at the very earliest stages of something that was clearly to become really big. I also think I was attracted to it because it involved people who were my peers, who were mostly my age. We were dealing with this life-changing diagnosis and early death.”
Daar’s workdays begin at home at 3 a.m. At 4 a.m. he runs on the neighboring streets. Then he goes to work at The Lundquist Institute and makes his daily rounds of his patients at Harbor UCLA. He doesn’t stop for breakfast or lunch. He returns home about 7 p.m, eats dinner, reviews emails and is in bed by 10 p.m. He has not had a day off since he received the March 21 email from the National Health Institute.
“It’s an exciting time to do infectious disease work. It’s scary and it’s all hands on deck,” he said.
ER