Lessons Learned from COVID-19 and HIV/AIDs Pandemics with Richard D'Aquila, MD
Accelerating new advances in the prevention, diagnosis and treatment of infectious diseases is an important goal of the Northwestern University Clinical and Translational Sciences Institute (NUCATS) and the past two years have been a crucial time for the study of infectious diseases. Richard D’Aquila, MD, professor of Medicine in the Division of Infectious Diseases at Northwestern and director of NUCATS, discusses some milestone discoveries made and recent lessons from the COVID-19 and the HIV/AIDs pandemics.
“Probably the biggest lessons are around mRNA vaccines, because they were being developed for many, many years – 20-plus years prior to the pandemic – and they were being studied for HIV as well as for earlier coronaviruses and other viruses. But, it was the scale of the COVID-19 pandemic that allowed such very rapid and robust research that we've learned a lot.”
— Richard D’Aquila, MD
- Associate Vice President of Research
- Senior Associate Dean for Clinical and Translational Research
- Director, Northwestern University Clinical and Translational Sciences Institute (NUCATS)
- Howard Taylor Ricketts, MD, Professor
- Professor of Medicine in the Division of Infectious Diseases
- Member of the Robert H. Lurie Comprehensive Cancer Center
D’Aquila is a prolific HIV/AIDS scientist with more than thirty years of experience. He became director of NUCATS just before the COVID-19 pandemic began and shares how HIV/AIDS research is running parallel to ongoing COVID-19 research with interesting crossover and lessons learned.
Topics covered in this show:
- mRNA vaccines have been a major category of comparison between the HIV/AIDS and COVID-19 pandemics. mRNA vaccines have been studied for 20 years prior to the pandemic for both HIV/AIDS and other viruses. D’Aquila says the genetic variation for HIV is astronomically higher than COVID-19, which has been a major obstacle in developing a vaccine, but mRNA research for COVID-19 has accelerated this research.
- While there is not presently an effective vaccine for the HIV virus, there are medications that can keep the HIV virus suppressed. However, D’Aquila says the body consequently remains in a state of chronic inflammation, leading to premature aging and earlier onset of conditions like heart failure, stroke and lung cancer. This makes the cure for HIV especially pressing.
- He says there have been three successful attempts to cure HIV so far. The first two cases included highly specific bone marrow transplants which happened to also prevent further HIV infection in cancer patients with a rare genetic condition. This strategy made use of the graft versus host reaction to help kill both cancer and HIV-infected cells, yet was very high risk due to extended lower immunity.
- The third cure of HIV was an advance that protected the patient's immunity while the new immune system was growing. It used immunity cells from umbilical cords, and because there are more repositories for umbilical cord stem cells and thus a wider variety of immunity cells, the likelihood for stem cell compatibility increased. It was also confirmed that a graft versus host reaction was not necessary to cure HIV, according to D’Aquila.
- Medicines called latency reactivating agents, or LRAs, are being studied at Northwestern in Ali Shilatifard’s lab. These medicines activate latent viruses otherwise left untreated by therapies so that they can be purged and support better containing viruses.
- When a virus changes so quickly, it can develop a resistance to medicines, D’Aquila says. This is a primary obstacle when developing medicinal treatments for COVID-19, specifically regarding the use of protease inhibitors which were previously used for HIV.
- Previously, COVID-19 viruses were not mutating in predictable patterns. However, the Omicron variants are developing within a linear sequence, which is hopeful, D’Aquila says.
- NIH launches clinical trial of three mRNA HIV vaccines
- Nature article: Woman cleared of HIV after transplant with umbilical-cord blood
- Read the NUCATS 2021 Impact Report
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Recorded on May 5, 2022
Erin Spain, MS [00:00:10] This is Breakthroughs, a podcast from Northwestern University, Feinberg School of Medicine. I'm Erin Spain, host of the show. The past two years have been a critical time for the study of infectious diseases. Accelerating new advances and prevention, diagnosis and treatment of diseases is an important goal of the Northwestern University Clinical and Translational Sciences Institute, known as NUCATS. Here to discuss lessons learned from the COVID-19 pandemic and other ongoing pandemics is Dr. Richard D'Aquila, professor of medicine in the Division of Infectious Diseases and director of NUCATS. Welcome to the show.
Richard D’Aquila, MD [00:00:53] Hi, Erin. Thanks for having me.
Erin Spain, MS [00:00:55] You know, you became the director of NUCATS right before the COVID-19 pandemic began. And this was a very interesting time for you. Your background is HIV/AIDS research. And now here we are with a new infectious disease. Take me back to the beginning of the pandemic and how you were able to use your background to get the institute started on the right foot when it came to studying COVID-19.
Richard D’Aquila, MD [00:01:21] Well, there was a lot of shifting from one foot to the other, and I was lucky to have been involved in HIV research my entire career. And we have a very strong center for AIDS research here called the Third Coast Center for AIDS Research. And a lot of what had been going on, on HIV research was a lesson for what we needed to do with COVID-19. And I think there's also a lot that we learned from COVID-19 that we're now beginning to think about applying to HIV. Nobody really understood how this virus was being transmitted in the early days, and that harkened back to the very early days of what was initially not even called AIDS. Long before we recognized that a virus caused HIV infection, there were all kinds of theories and people were scared. And as an infectious diseases fellow, I had to be delivering trays of meals into patient rooms because nobody else would go in. We learned much more quickly with SARS-CoV-2 than we did around the early days of the AIDS epidemic. But then again, everything has been accelerated. All of science moves at breakneck speed right now. I think the things that we had to do both to wind down research and really prioritize only research related to COVID-19. And then once it became safer in the surge, first couple surges had passed, all the reactivation. That was really hard but really made possible by all the great people in NUCATS. Our clinical research unit did a great job keeping going high priority research, but also helping researchers to do things remotely or do things outside. There were all kinds of innovations being done.
Erin Spain, MS [00:03:12] I want to drill in a little more to these lessons learned. Of course, you said you were able to come in to the COVID-19 pandemic with this knowledge, over 30 years of experience of working with HIV and AIDS. But what did you learn from COVID-19 that now you're able to apply to your HIV research?
Richard D’Aquila, MD [00:03:31] Probably the biggest lessons are around mRNA vaccines, because they were being developed for many, many years, 20 plus years prior to the pandemic, and they were being studied for HIV as well as for earlier coronaviruses and other viruses. But, you know, it was the scale of the COVID-19 pandemic that allowed such very rapid and robust research that we've learned a lot. And one lesson that it's still preliminary, and I think there's a lot more to be studied about it, but I think everyone's heard how vaccination using proteins from the well, mRNA, encoding proteins from the original strains has actually led to broad immune responses against these evolving variants of concern. And yes, it's not as good, but it's, it's actually to an immunologists and virologists remarkable that it's as good as it is. For HIV the problem is the genetic variation, how much the virus changes, is astronomically higher than for COVID-19. And that's been the biggest problem in developing a vaccine against HIV. And the way we've been thinking about it, all the efforts been dedicated to exposing the immune system to different kinds of vaccines that look like different kinds of viruses that are around the world causing HIV infection. And it's really hard because there's so many different variants, so you can't cover them all. But what we're going to try now with mRNA vaccines, learning the lesson from COVID-19, is maybe you don't have to have a lot of different vaccines. Maybe it's a question of with the mRNA, it's a better adjuvanted it stimulates the immune system better. So maybe just repeated vaccinations with something similar will do a good job. This is still a speculation, but it could, if it works, it could revolutionize the very frustrating, very long search for an HIV vaccine.
Erin Spain, MS [00:05:46] That's so exciting, because there have been these breakthrough news stories about, oh, recently a woman who was cured of HIV using immune cells from an umbilical cord. But there are some caveats there. This may not work for everyone. Tell me what's happening right now and why the need is still so great for a universal vaccine.
Richard D’Aquila, MD [00:06:08] Well, let's break down vaccine and cure, because they're very, very different things. So a vaccine is intended to prevent infection in the first place. We already have lots of ways to do that behaviorally using condoms, testing. But people are not perfect and those things aren't always done. So we still need a vaccine. The cure issue is very different because now when someone is infected, we do have very effective medications that keep the virus suppressed, that keep it from causing damage to the immune system over years. So, people who have HIV infection now and they if they get on their medicines, if they consistently take their medicines, and that's now easier to do than it was few years ago, if they can stay on the medicines, the virus doesn't harm the immune system in the ways that it used to by causing all these terrible, rare infections and cancers. However, the medicines don't get rid of the virus. So, what that means is for reasons that we're still studying, and don't fully understand, the immune system is working overtime. So, there's a state of what's called chronic inflammation, which leads to premature aging. So, people who have very well treated HIV, age maybe 10 to 20 years, more quickly than uninfected people do, which means the biggest problems in HIV care right now are the diseases that hit everyone over age 65 or 70. But they're hitting people living with HIV at much younger ages. So, now, the leading cause of death for people with HIV is lung cancer. And there are all kinds of earlier onsets of different kinds of heart disease, heart attacks and strokes, heart failure. Everything that happens when you get older happens earlier with HIV. So that's the main reason why I think it's really important to try to cure the infection, because the hope is if we can stop the infection from smoldering, the medicines are great at keeping the lid on it, but they don't get rid of it. So, if we can completely get rid of it, maybe then we won't have this premature aging as as well. So, there have been a lot of efforts to try to cure HIV. There actually have been three people who have been cured by these efforts. And this woman that you mentioned there was in the press recently was the most recent, and the other two were men. They all had a very drastic strategy used to cure HIV. They all had severe cancers that required what used to be called a bone marrow transplant. They had to have that to save their life from the cancer. But the first time this was done, there was a very smart doctor who realized there are very rare people, mostly in northern Europe, Scandinavia and northern Germany, who have deficiencies in both alleles, both genes that encode for the receptor, one of the two receptors that HIV needs to get into cells and infect cells. So, they got bone marrow cells from these individuals who had this genetic defect. That meant that when those bone marrow cells repopulated, the recipient who'd had their complete immune system wiped out so that they could get it repopulated with someone else's immune system. Well, the new immune system doesn't allow HIV to enter any of the cells that it normally infects. That was the trick to curing them. But it's simply not feasible to do that. And the risks are severe. The first patient who had this was in an ICU for months suffered a stroke as a result of all the work. And so the most recent case was in advance for a couple of reasons, because they learned how to cover the patient's immunity while the new immune system was regrowing so that there wasn't this weakness of impaired immunity for a few months. This new approach using umbilical cord stem cells, makes cells more available, because it's easy to collect cells from the umbilical cord. And there are bigger repositories of that than of voluntary donations of bone marrow, for example. But then not having immunosuppression for as long was a benefit. And the third scientific lesson that we learned from that case was in the first two cases, the and grafted new immune system had what's called a graft versus host reaction. That meant that it attacked the recipient of those cells. And that's actually a benefit in treating cancer because it helps to attack any remnant of the cancer. And it was thought that that might have also helped get rid of any residual HIV infected cells that hadn't been completely gotten rid of. But in this case, that didn't happen because it was a kinder and gentler approach. And so what we learned is you don't need that in order to cure HIV. You don't need to have the graft actually start attacking the patient.
Erin Spain, MS [00:11:34] This really isn't feasible for all the people out there who are living with HIV.
Richard D’Aquila, MD [00:11:40] There are things being worked on that may someday become feasible. There's been a big effort to develop medicines that are called latency reactivating agents. We use the term LRAs and we have some really interesting research going on here at Northwestern, a collaboration with some of my colleagues in infectious diseases, with Ali Shilatifard's Lab in biochemistry and molecular genetics, Judd Hultquist in ideas, the person collaborating with Ali's lab. And there the idea is there are these latent viruses of latent HIV that's sleeping during the time when people are on the medicines. So, the medicines don't get rid of it. And if you stop the medicines a couple of weeks after stopping them, this these sleeping viruses come back. So, the idea that's been worked on is to try to find something that will wake them all up while the medicines are still on board, so that then that virus has nowhere to spread to in the body. And you could, what we call, purge the reservoir and get rid of all of the viruses that are latent. The problem is we don't really have good medicines that wake up all the viruses. And also we were hoping that when those viruses woke up, the immune system would recognize the cells that were infected by those viruses and kill those cells. What would, it turns out, is those cells wake up, the virus wakes up in those cells, it makes new virus, but the immune system doesn't kill those infected cells. So then they go back to sleep again. So, a lot of labs, including mine, are trying to work on alternate ways. Then this latency reactivation approach, it's still very, very early, but there are hopes that we could boost other aspects of the immune system that now HIV basically preempts. And it's always a chess game between the virus and the host. So, we want to make a smart move so that we can counter the virus countermeasures and get around it. So, the virus normally depletes some very effective immune responses. So, we want to figure out ways to replete them and then stop the medicines that block HIV so that then the body's natural defenses might be able to be strong enough to keep it at bay, maybe not completely get rid of it, but more carefully contain it, better contain it than the medicines do now. And this is a stepwise approach. Once we learn how to contain it, then we can figure out other ways to try to attack it even more.
Erin Spain, MS [00:14:26] You talked about some lessons learned as far as developing a vaccine for HIV, things that we learn from COVID-19. Are there some other parallels or things that maybe folks haven't thought about that you're looking at in the scientific community, comparing and contrasting things that you've learned during this time?
Richard D’Aquila, MD [00:14:45] The other lesson that scientists are only beginning to talk about now is around treatments for viruses. So, I've been talking about all these medicines that we have now to treat HIV. I was involved in developing some of the first of them. I was working in one of a few groups that figured out the trick that we needed to use three medicines, not one or two, and that that saves the day. The reason we needed to use three medicines for HIV and we need this for tuberculosis and some other infections, too, is because when a virus changes so quickly, it can develop resistance to a single or sometimes even two medicines. And it's not that the medicines are inducing resistance. The issue is the virus is always making tons of different mutations just to give it an opportunity to find an advantage. And so the medicines don't make the mutations, but they select for a mutant that is resistant to them. Medicines for HIV that have helped us a lot are called protease inhibitors. We don't use them very much anymore because we have medicines that are even better. But a protease inhibitor that was basically developed following the lessons learned from developing HIV protease inhibitors is now available for treating COVID-19, and it's called paxlovid. The concern that scientists are starting to have, and this is theoretical, but the concern is that if we use a lot of this, could the virus develop resistance to this one medicine? Number one, we have to be careful to use it the right way and to make sure that it's being effective. There are people already studying if we need to add another medicine to it to make it more bulletproof against resistance. But the big issue and a big problem is unlike for HIV, where we could study the virus in the laboratory and put resistance mutations into the virus in the laboratory and study how to stop those resistant viruses. It's not allowed to genetically engineer mutations into the virus that causes COVID-19 because we don't want to take any risks. Right. But somehow we're going to have to get smart and figure out a way to study resistance and learn to get ahead of it, to learn how to stop it before it becomes a problem.
Erin Spain, MS [00:17:15] Right. Because maybe that's something that even the general public isn't thinking about. Like we keep thinking that we're getting over the hump or and then a new variant comes in. We are not in a safe zone yet as far as what could happen with this virus. Is that right? As far as mutations?
Richard D’Aquila, MD [00:17:31] You know, I'm keeping my fingers crossed. The evolution of the variants of concern up until this point in time has been such that they weren't evolving in a predictable and linear way one from another. So especially Omicron just came out of left field. We don't know where it came from, and it was so totally different. But what's been happening since the start of 2022 is that we're seeing Omicron variants evolve in a kind of linear sequence, and it's a lot more like how influenza evolves with what we call genetic drift. So far, it looks a lot more like how other viruses evolved. Not these big random jumps that we saw earlier. I don't think it's out of the question that we'll see another random jump, but there's also increasing immunity. It's not where we want it to be, but maybe it's at a point where now this virus is beginning to behave more like other viruses that humans have seen before. We'll just have to wait and see. The thing that we do have to look out for, and it's what you said, Erin, is a new variant going to pop up that's different, that causes more severe disease, that better evades immunity, that's resistant to the medicines or the monoclonal antibodies that we use for treatment. And so what I tell everybody is just pay attention. Everything is being monitored closely. Science is going to let us know an early warning. And right now, we're in a safe zone. But you can't let your guard down. You got to listen to what's going on and keep your mask in your back pocket. You may have to pull it out one day.
Erin Spain, MS [00:19:13] We've covered quite a few topics here about lessons learned from COVID-19, applying them to HIV and things we learned from HIV to apply to COVID-19. What would you like to leave the audience with today?
Richard D’Aquila, MD [00:19:24] There's another parallel. Some of my colleagues here at Northwestern are very active in this kind of work. These viruses both affect people who are vulnerable. And that means people who suffer from socioeconomic and structural and systemic racism. And I would say that also is not just races and ethnicities, but it extends to sexual and gender minorities as well. And there's no excuse for that justification for that. And we should not be tolerating it. And we need to end all of these inequities.
Erin Spain, MS [00:20:00] Thank you so much, Dr. Richard D'Aquila.
Richard D’Aquila, MD [00:20:03] Thanks, Erin. It's been fun. I loved your questions.
Erin Spain, MS [00:20:15] Thanks for listening and be sure to subscribe to this show on Apple Podcasts or wherever you listen to podcasts and rate and reviews. Also for medical professionals, this episode of Breakthroughs is available for CME Credit. Go to our website feinberg.northwestern.edu and search CME.
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Physicians who listen to this podcast may claim continuing medical education credit after listening to an episode of this program.
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At the conclusion of this activity, participants will be able to:
- Identify the research interests and initiatives of Feinberg faculty.
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The Northwestern University Feinberg School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
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The Northwestern University Feinberg School of Medicine designates this Enduring Material for a maximum of 0.25 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Richard T. D'Aquila, MD, has nothing to disclose. Course director, Robert Rosa, MD, has nothing to disclose. Planning committee member, Erin Spain, has nothing to disclose. Feinberg School of Medicine's CME Leadership and Staff have nothing to disclose: Clara J. Schroedl, MD, Medical Director of CME, Sheryl Corey, Manager of CME, Allison McCollum, Senior Program Coordinator, Katie Daley, Senior Program Coordinator, Michael John Rooney, Senior RSS Coordinator, and Rhea Alexis Banks, Administrative Assistant 2.