For more than a year now, COVID has been society’s focus—and rightly so. But today we turn our attention to another virus—HIV. After 40 years, there is still no cure or a vaccine for the disease. In this episode, we hear from Dr. Anthony Fauci and CEO of innovative company American Gene Technologies, Jeff Galvin, about the past, present, and future of HIV treatments and medications. Is there a cure on the horizon? Guests: Jeffrey Galvin, American Gene Technologies Anthony Fauci, National Institute of Allergy and Infectious Diseases
For more than a year now, COVID has been society’s focus—and rightly so. But today we turn our attention to another virus—HIV. After 40 years, there is still no cure or a vaccine for the disease. In this episode, we hear from Dr. Anthony Fauci and CEO of innovative company American Gene Technologies, Jeff Galvin, about the past, present, and future of HIV treatments and medications. Is there a cure on the horizon?
Guests:
Jeffrey Galvin, American Gene Technologies
Anthony Fauci, National Institute of Allergy and Infectious Diseases
Michelle McMurry-Heath (00:06):
For more than a year now, COVID has been society's focus, and rightly so. We've seen its impact on our health, our economy, and our way of life. We've witnessed new vaccines developed in record time. And now, we're in a race to get the entire globe vaccinated before more virus mutations occur. But today, we turn our attention to another virus, one that's been around since long before COVID upended our lives, and that is the human immunodeficiency virus, or HIV. We have yet to discover a cure or a vaccine for HIV. But over the course of 40 years, we've developed treatments that have turned it from a certain death sentence to a manageable chronic illness for many, particularly those with access to these innovations.
Media Clip (01:04):
I want to know why it takes five to 10 years in this country to test drugs that you can test in Europe in a third of the time. We are simply asking the FDA to do it quicker.
Anthony Fauci (01:18):
We have a vaccine against coronavirus in 11 months, and we've been trying for decades to get it against HIV.
Michelle McMurry-Heath (01:33):
Today, we will talk about how treatments have evolved over time and how biotechnology may hold the key to a cure. I'm Michelle McMurry-Heath, and you are listening to, I am BIO.
In the summer of 1981, the morbidity and mortality weekly report, or MMW, described instances of young, otherwise healthy, usually gay men, dying quite suddenly. There were speculation about what it could be, but nobody had an answer.
Media Clip (02:16):
Scientists at the National Centers for Disease Control in Atlanta today released the results of a study, which shows that the lifestyle of some male homosexuals has triggered an epidemic of a rare form of cancer.
Michelle McMurry-Heath (02:35):
Dr. Anthony Fauci remembers first learning about this mysterious infectious disease in 1981. He described that moment to Julie Gerberding during BIO's international convention this past June.
Anthony Fauci (02:50):
Well, Julie, I remember it extremely clearly, almost exactly what I was planning to do the next day after the MMW report came out. I was sitting at my desk and building 10, which is the clinical center of the NIH, our hospital, where we study patients. And I remember sitting in my office on the 11th floor of building 10, seeing the first MMWR in June of '81. 5 gay men, all from LA, curiously previously well and all gay with this extraordinary situation of pneumocystis pneumonia, which I know you never see in a normal person. So why would they be having pneumocystis? I put it aside thinking it was a fluke. There must have been something going on, some drug that they took, some poppers to influence their immune system and suppress it.
Anthony Fauci (03:44):
Then, the second MMWR, which I remember it very, very emphatically because it changed my life, Julie, it landed on my desk, July, 1981. Now, 26 men, curiously all gay, not only from LA, but from San Francisco and New York City, not only with pneumocystis, but with other opportunistic infections as well as [inaudible 00:04:11]. I can tell you, I can still feel what I felt that day. I felt a chill up and down my spine saying, "Oh my God, this is a new disease, a new infection." Because having been in the infectious disease circles for the previous nine years, I had never seen anything that even remotely resembled this. And I said, "I'm going to change the direction of my career," and I did.
Michelle McMurry-Heath (04:37):
Even though researchers like Dr. Fauci began working to treat the disease almost immediately, for years, HIV was regarded as an open secret. If you had it, you didn't talk about it. But things started to change in the late 1980s when Princess Diana and other celebrities began to sort fact from fiction during public appearances, like this one featured by the BBC.
Media Clip (05:03):
Princess Diana demonstrated that she cared because she took everybody's hand. This was Diana, the Princess of Wales, coming in gloveless and shaking our patient's hands, as well as ours. That was very moving.
Speaker 3 (05:22):
The ward can take 12 patients. Today though, the beds were empty. The patients were hiding from the media, unhappy at the way they've covered the AIDS epidemic in the past. Finally, one did agree to a picture of the princess shaking his hand to prove you can't catch AIDS through casual contact.
Jeff Galvin (05:40):
I don't think it took a lot of convincing for him, because he was dying. And he thought, "Well, so what? I'll do it." On the night it aired, I got lots of notes pushed onto my door. It's very, very moving, and I never got any negative reaction from the public at all. If a Royal was allowed to go in and shake a patient's hands, somebody at the bus stop or in the supermarket could do the same. That really educated people.
Michelle McMurry-Heath (06:13):
In March, 1987, AIDS activists were calling for the FDA to develop something that could save lives. AIDS activist, Eric Sawyer, talks about it in a video for the United Nations program on HIV/AIDS.
Media Clip (06:29):
Our first demonstration was on Wall Street in 1987 in March. The activist movement that was really birthed then and exploded because there were so many dying of AIDS.
Media Clip (06:43):
I want to know why it takes five to 10 years in this country to test drugs that you can test in Europe in a third of the time. We are simply asking the FDA to do it quicker.
Michelle McMurry-Heath (06:57):
Activists like Eric were more important to the drug development process for AIDS than most people realize. Dr. Fauci explained the epiphany that changed his approach to AIDS research.
Anthony Fauci (07:10):
Well, what happened back then, as you may remember, is that we were dealing with uncharted waters. We had a disease that had no treatments at all, and treatments were mostly in the clinical trial arena. And we had people who knew that they were going to die before the cumbersome process of a clinical trial and the even more cumbersome process of regulatory approval would take place. So they wanted to be at the table when we discussed the design of trials, the access to trials, the inclusion and exclusion criteria, how long it takes to get a drug approved. And why can you not get drug outside of the arena of a clinical trial, what we called parallel track? All of those things, they wanted at least-
Anthony Fauci (08:03):
All of those things they wanted at least to be heard, but the rigidity of the scientific community, as well as the regulatory community, weren't listening. "We know better. We're scientists. Don't tell us what to do." That was the attitude back then. So they needed to gain our attention, and since I was a visible figure out there doing my best to probe what's going on, to involve in the community, I became the face of the federal government. So when they decided they wanted to get the attention of the federal government by iconoclastic, disruptive, theatrical ways that they did with organizations like ACT UP, I became a target. Well, one of the best things I've ever done in my life was instead of pulling back the way many of the scientists and people in the regulatory community did, and running in the other direction when they saw the demonstrations, I started to listen to what they were saying. And what they were saying was making absolutely perfect sense. And I said to myself, "You know, if I were in their shoes, I'd be doing exactly what they're doing," because they weren't asking for anything crazy.
Anthony Fauci (09:24):
They were asking just to be heard. So that's when I called them in, literally in this room where I'm sitting in this conference room, and sat down and said, "We need to talk." We didn't settle all the problems then by any means, but we opened up a dialogue. And over a period of time, I went from a listener to a colleague, to an advocate, to an activist because they were absolutely completely correct. And the contributions that they've made to how you do research and you do regulation in the context of an ongoing outbreak, I think right now, has written the book on community involvement in how the scientific and regulatory community interacts with those people that are involved. Of note that those same people who are outside this window here storming the NIH are now some of my closest personal friends as it were, and they are helping us in the outreach with COVID-19, because they have decades of experience of how to do that. So they become partners now in that.
Michelle McMurry-Heath (10:45):
In March 1987, the first drug for HIV, zidovudine, or AZT, was approved. Dr. Fauci describes AZT and some of the medications that followed it.
Anthony Fauci (10:57):
It was the first and only placebo- controlled trial of a single drug, and that was AZT against placebo in people who had a prior history of pneumocystis pneumonia. That was the entry criteria, which seems so strange right now that that was the entry criteria. And what you had, the end point was either death or another opportunistic infection. And in the placebo group, there were 19 deaths, and in the treatment group, there was one death. And the FDA made the fastest in their history approval of a drug. There was an incredible amount of hope. We now have a drug. But we all realized deep down, even though we were very pleased about it, that this was a single drug with an RNA virus that replicates and mutates very easily. And although some people continued to do well just on AZT, the majority of people had a temporary improvement and then things went down.
Michelle McMurry-Heath (12:00):
In 1996, another breakthrough drug was developed, Dr. Fauci told Dr. Gerberding.
Anthony Fauci (12:06):
Between 1987 and 1996, we were playing with different combinations, usually two drugs. The best one was lamivudine that came in. So lamivudine with AZT did pretty well, but it was the transforming year of 1996 at the famous Vancouver meeting, where two or three of the studies using protease inhibitors in triple combination from multiple pharmaceutical companies, including Merck. Well, one in which we presented results, which was stunning. The first time ever that you had a durable control of virus, and people were literally transforming in their clinical course. We were calling it the Lazarus effect. I remember that so clearly, where people who were in hospices and people who were getting ready to die were all of a sudden starting to feel well again. It was one of the greatest triumphs in clinical medicine and its relationship to basic and clinical research. I mean, it is something that younger fellows that you and I now interact with, we really should continue to tell them the story of what it felt like going through dark years and then having the clouds move away. Amazing.
Media Clip (13:38):
The Scientific Advisory Panel has recommended that the Food and Drug Administration approve a new drug called the most important advance since AZT.
Media Clip (13:47):
New York, which has the highest number of AIDS patients in the country, has shown a dramatic decrease in the number of AIDS deaths, a 30% drop.
Michelle McMurry-Heath (14:03):
From beginning with a singular drug that delivered only temporary results, today, there are dozens of FDA-approved medications that make HIV manageable for people who have already contracted it. And since 2012, pre-exposure prophylaxis, or PrEP, has been available for adults who are at high risk for contracting HIV. However, none of these treatments offers a perfect solution. The Kaiser Family Foundation estimates that there are about 35,000 new HIV cases annually, and people are still dying from directly-related causes. For many, the question is: If we can have effective COVID vaccines available in less than a year, why haven't we found the solution for HIV?
Anthony Fauci (14:53):
When you look at natural infection, if the body generally is able to handle natural infection even with diseases that have a high degree of morbidity and mortality, smallpox, measles, polio, at the end of the day, even though people suffer and die from those diseases, the majority of people recover because their immune system essentially handles the pathogen, removes it, and gives you lifelong protection against the identical pathogen. We've never had that with HIV, because the body does not make a good immune response against HIV, and so we've never proved the concept that it could be done. We have a vaccine against coronavirus in 11 months, and we've been trying for decades to get it against HIV, but a very important story in the relationship between HIV and coronavirus regarding vaccines. The coronavirus researchers have partnered with the structural biologists who were doing HIV, and learned from them how-
Anthony Fauci (16:03):
... HIV and learned from them how you stabilize a molecule in it's pre-fusion, highly emetogenic form by doing certain mutations. So they took the spike protein and did exactly what the spike protein what the HIV people were doing with the Envelope Trimer. They stabilized it in it's pre-fusion, highly emetogenic form and that turned out to be the optimal immunogen for a Coronavirus. So it was AIDS researches which set the stage for a successful vaccine against SARS-CoV-2. Same thing with the platforms, the adenovirus platform that's in the J&J. That was started off with HIV vaccines, with the Ad26. So there's so much cross fertilization between the research of HIV and SARS- CoV-2.
Michelle McMurry-Heath (17:03):
You've seen Coronavirus mutate and grow stronger before our eyes. The HIV virus is even faster and more unstable. However, a small company based out of Maryland believes they might have a cure. We'll talk about it in a moment. Are you signed up for Good Day BIO? It's the daily five minute newsletter at the intersection of biotech, politics and policy. Become a subscriber today at bio.org/goodday.
Media Clip (17:51):
I would say to HIV that you are an intruder, you are here for a ride, but you don't belong to me. Don't get comfortable because every piece of me is trying to expel you. And I'm going to continue that until I die. And you will not be the cause of it.
Michelle McMurry-Heath (18:14):
American Gene Technologies or AGT, is a company working on what they hope will be a cure for HIV. We spoke with the CEO.
Jeff Galvin (18:24):
My name's Jeff Galvin, and I'm the CEO of American Gene Technologies. And we call it AGT for short. We are an advanced gene and cell therapy company, developing a platform of components that can be utilized to efficiently create new therapeutics and cures within this tremendous emerging market of gene and cell therapeutics.
Michelle McMurry-Heath (18:50):
Jeff gave us some insight into gene therapy and why AGT decided to focus on HIV.
Jeff Galvin (18:57):
The first thing we did was to develop a platform of components that could be used as sort of the starting point. So these components are common across many different diseases. And so they form building blocks that can be the foundation of, today, literally hundreds of cares, but in the future, probably thousands. And then we looked around and tried to figure out, okay, based on the components that we had today, what were the highest value diseases that look the most reachable and the most likely to make it through the clinic? And it turned out HIV was number one. So what we did is we started to design from solution backwards, how would you cure an HIV person?
Jeff Galvin (19:40):
And what we decided is that you want to create an immune system in that patient that's capable of battling HIV just like your immune system battles every different type of virus that could get into your body, because you're aware that even if you get COVID, you have COVID T cells in there that start to react. And the same, thing's true about a cold or the flu and most viruses you can get over on your own.
Michelle McMurry-Heath (20:05):
Jeff explains why curing HIV has escaped scientists and inventors for decades.
Jeff Galvin (20:13):
HIV has got a special capability of penetrating the very immune system that is there to protect you. It actually is the, it's target is the Sentinel T cell that is the first one to arrive at the pathogen to detect it and create an entire immune cascade against HIV. That's called an HIV-specific CD4-positive T cell. Sounds very technical, but think of it as the conductor of the immune orchestra. And it's a specialized T cell that comes in every different format. And you have literally millions of different types of T cells in your body that have different antigen receptors that are looking for foreign proteins on invaders. They could be looking for cancer even, but they could be looking for bacteria or viruses or other types of things that could end up in your body and they are ready to fight it.
Jeff Galvin (21:06):
So the one that is tuned for HIV will go ahead and run right over to the HIV virion, but instead of killing the virion like it's supposed to, the virion grabs onto it and merges with the cell, injecting its DNA into the very Sentinel T cell that was there to alert your body to the pathogen. So now that Sentinel T cell is no longer protection, it is actually the beachhead of the infection. It runs to the lymph nodes and replicates, and then it starts to spread HIV all over your body, the exact opposite of what it was supposed to do.
Michelle McMurry-Heath (21:41):
So that's how HIV behaves in the body. This is how AGT may be able to cure it.
Jeff Galvin (21:49):
So what we can do though, is we found out, and this is theory and experiments and data that has been now for almost 20 years. That certain people have a very hard time of getting infected with HIV because they're missing one little latch point on the outside of their T cells that HIV uses to grab tightly onto the membrane of the cell and merge with it, and when you remove that latch point, HIV has a hard time getting into that T cell, and guess what? The T cell does its job. It kills the virion, it alerts your body to the pathogen, you make an entire immune cascade against it, including antibodies and CD8 cells that clean up all the mutations, and those people don't get infected with HIV.
Jeff Galvin (22:35):
Now, it doesn't work on every form of HIV, but what we found is that by adding that protection to your T cells and a couple of other little tweaks that we do to the DNA of your T cells, we can make them impermeable to every known type of HIV. And therefore we can make you permanently immune to HIV. Just like these people that are born immune to HIV, we can do that with gene therapy.
Michelle McMurry-Heath (23:04):
As Jeff emphasized during our interview, his company's technology remains unproven, but it appears promising. He explained how gene therapy is applied to AGT's approach.
Jeff Galvin (23:17):
Gene therapy is essentially, you probably know that viruses have been reprogramming your DNA for 1.5 billion years. Well, now we can crack open viruses, we can scoop out the bad information that's in those viruses that make you sick, and by scooping that out, we have an empty delivery vehicle that can deliver anything we want to your cell. So instead of delivering something malevolent, we can develop little genetic constructs that can be put into your cell that are benevolent, that improve the health of those cells. And that's what we're doing. We pull out your HIV T cells, we modify them in what's called ex vivo, to be impermeable HIV, we put them back in your body and you're immune for life.
Jeff Galvin (24:03):
... HIV, we put them back in your body and you're immune for life to HIV, and we can do it to somebody that's already HIV infected. So once they're well controlled on antiretrovirals, which is the normal treatment for HIV to prevent AIDS and prevent transmission, you take a pill every single day. It's a chemotherapeutic. It's very painful to take because it has all these side effects, but it prevents AIDS and it prevents transmission. Well, once you're on that for one to three years, you have HIV T cells back again. We can make you immune and that's all this process is.
Jeff Galvin (24:37):
This hasn't been proven yet. We think that within a couple of weeks, you can throw away all of your antiretrovirals and be normal for the rest of your life. You can never give HIV to anybody else. You can never get AIDS and you can never recontract HIV. HIV is out of your life forever. And there is a lot of experimentation in the past that shows that this should work and we're already in a clinical trial right now. We treated two patients and neither one of them has had any serious adverse events. So, we're already getting data back from the clinical trial that this is safe, and we think that we're going to start getting efficacy signal by the end of the year.
Jeff Galvin (25:14):
And by the middle of next year, we actually believe that we'll be able to take people off their antiretrovirals and see if they're in fact permanently immune from this treatment. And I feel cautiously optimistic is the official way of saying this. But I got to say, when you look at some of the data in the past, and you look at how much we've improved this process from those people that have been functionally cured, it would make you think that this might just work. And so we're very excited keeping our fingers crossed, but that's basically how this whole thing works.
Michelle McMurry-Heath (25:47):
If this works the way Jeff is describing, it would be monumental. The fact is that even though HIV can be managed, it's a burdensome, lifelong commitment to antiretrovirals.
Jeff Galvin (26:01):
Then let's talk about the people that were really focused on, the patients. How would you like it if you had to take a pill that reminded you every day that you had something in your body that you could never tell anybody around you about? Okay. So then one day you find out, you don't need to take that pill anymore, so you're not going to get any of those side effects. You won't be tired every day. You won't be nauseous every day. You won't have diarrhea anymore. You're not going to get early aging, bone density issues, all that stuff.
Jeff Galvin (26:33):
You're not HIV positive anymore. You can't give it to anybody. You can't get AIDS. You don't need any special medication, any special attention, nothing. Can you imagine how they'll feel? Now, remember, I have to be very careful about the way I talk about this cure. It's not proven yet. Like I said, I am optimistic that we can do this thing, but this has been the dream of HIV patients for 40 years. In the first 13 or 14 years, maybe even more than that, HIV was a death sentence. And then because of these drug cocktails, these inhibitors that go into these antiretroviral therapies, it's no longer a death sentence, but it's a life sentence of taking those drugs. This has returned to normal life. I mean, I'm afraid to ... I'm buried in emails from people saying, "Please let me into the clinical trial." And I have to explain to them, "Hey, it's not proven that it works yet. It's a limited clinical trial. It's only in two sites. We can't decide who in the clinical trial. All we have is trial sites. They decide who gets into the clinical trial. We never even know who they are." I just tell you it just tears your heart out.
Jeff Galvin (28:07):
I am so hopeful that we are seeing a light at the end of the tunnel of this, and we may actually have something that is probative next year that HIV can be cured.
Michelle McMurry-Heath (28:20):
This is the kind of innovative work we get really excited about at BIO. The ways our companies are truly changing the world, helping people live longer, healthier lives and making the impossible possible. We will be following AGT's journey to see how this potential cure pans out. Make sure to subscribe, rate and/or review this podcast and follow us on Twitter, Facebook and LinkedIn @iambiotech and subscribe to GoodDay BIO at bio.org/goodday. This episode was developed by executive producer, Theresa Brady and producers, Connor McCoy, Cornelia Poku, and Marilyn Sawyer, sound design and mixing by Jess Fenton, theme music created by Luke Smith and Sam Brady.
Michelle McMurry-Heath (29:19):
On the next episode, we will be discussing the ever contentious conversation around drug pricing. How can we ensure that misguided policies don't compromise innovation? We dig in and talk with the experts. See you in two weeks.