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Interviewer: The University of Utah is home to the only Ryan White-sponsored HIV clinic in Utah, treating up to 90% of Utahan HIV patients. We're joined today by two doctors from the clinic to speak on what that clinic offers.

Announcer: Health tips, medical news, research, and more for a happier, healthier life. From University of Utah Health Sciences, this is The Scope.

Interviewer: We're sitting down with Dr. Claudia Goulston. She is an Associate Professor in Infectious Diseases, and Dr. Rosado, who is the Medical Program Director for the Ryan White Program. When it comes to HIV and AIDS treatment and diagnosis, and things like that, where does the Ryan White Program fit within the Salt Lake community?

Dr. Rosado: So the Ryan White Program, basically, the purpose of this program is to treat people who are HIV infected and are unable to pay for HIV therapy, because the HIV therapy is very expensive even in this country. We also have funding to do HIV testing mainly for partners of our patient, spouses, and anybody who wants to have an HIV test, we can do that using Ryan White funding.

Interviewer: So, Dr. Rosado, how many people do you see here in Salt Lake?

Dr. Rosado: In the clinic, we had about 1,600, 1,700. It depends. Patients that come to our clinic, not all of them are Ryan White patients because we see people who are Medicare, Medicaid, or they have primary insurance. That's the total of the 1,600 patients. But people who quality for Ryan White is about 500 patients that receive Ryan White funding.

Interviewer: And Dr. Goulston, why is a program like this important for a population like this?

Dr. Goulston: Well, many people are uninsured or underinsured, as the case may be, and so it kind of dovetails with that. And we have all sorts of providers within the clinic that work as a medical home to help get patients care. So we have case managers that can help treat patients and get them into care. We have counselors, psychiatrists, OB-GYN, neurology in our clinic as well and we work with all these different subspecialties to try and give them the best care possible.

Interviewer: So that sounds like a pretty comprehensive care. So that's at Clinic 1A? Is that important for the treatment? It's not just medication, it's everything else?

Dr. Rosado: Well, again, we offer a comprehensive HIV care to our patients and we try, as Dr. Goulston mentioned, to have a medical home model so the patient can come to that clinic and they can see the HIV provider. If they need to see psychiatric care, mental health, neurology, or OB-GYN, we have all those services in the clinic.

Interviewer: I mean, programs like Ryan White where you can get these new treatments and things, it . . . I mean, treatment is not like it was 20, 30 years ago, right?

Dr. Goulston: Not at all.

Interviewer: How has it changed?

Dr. Goulston: Well, now, we have many regimens that are single-drug or single-tablet regimens once a day. We have much lower side effects and very effective, and it is much more tolerable for patients to take and to remember. We used to have treatments that could be up to five times a day with miserable side effects, and those days are gone.

Interviewer: So it's not a death sentence anymore either, right?

Dr. Goulston: If you take your meds and can afford them and can carry through, then people can live.

Interviewer: So Clinic 1A . . . So it's treatment. Do they offer services for prevention?

Dr. Rosado: We do. In Clinic 1A, we do offer clinic services for prevention. But we need to emphasize here that the Ryan White Program doesn't pay for TRUVADA for prevention or HIV PrEP, because the funding for Ryan White is for people who are HIV infected. But we do see patients that are taking PrEP, TRUVADA, to prevent HIV. Usually, these people have their own insurance. And the company that makes TRUVADA, Gilead, they do have a patient assistant program. If a patient is unable to pay for the medication, they can offer the medication for free as long as the patient qualifies.

Interviewer: So say a listener who might be HIV-positive, underinsured, or not even have insurance, where they can go get more information for the Ryan White Program?

Dr. Rosado: Now, these people can go online and Google "Ryan White" and they will get all the information they need. In Utah, they can call the University Hospital Clinic 1A and we can offer them more information about Ryan White. We see anybody who wants to come to the clinic, and I need to mention, including people who are undocumented. As long as they are a Utah resident, they qualify for the Ryan White. And the reason I say this is Ryan White is present in every single state. The only qualification will be that you have HIV and you reside in that specific state, and you are unable to pay for your medication. The Ryan White, definitely, will cover your HIV therapy.

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Interviewer: New FDA approved oral medication that has been shown to prevent transmission of HIV, we're talking about PrEP today on The Scope.

Announcer: Health tips, medical news, research, and more for a happier, healthier life. From University of Utah Health Sciences, this is The Scope.

Interviewer: We're here with Dr. Claudia Goulston. She is the associate professor in infectious diseases, and she is a HIV specialist. When it comes to HIV, prevention is huge, right?

Dr. Goulston: Correct.

Interviewer: Because I've been hearing that it's what, 40,000 new cases in America each year?

Dr. Goulston: That's the ones that are known.

Interviewer: Why did you specify that? Are there tons that aren't known?

Dr. Goulston: Potentially, there's a lot more than that. They actually estimate around 50,000 at least.

Interviewer: And that number doesn't seem to be changing. Why is that?

Dr. Goulston: No. Because even though we prevent cases, some people are not on medications and some people also don't know that they're HIV positive, and so their risk is high and spreading it to other people.

Interviewer: When it comes to prevention, what is the tried and true best way to prevent infection?

Dr. Goulston: Condoms, first.

Interviewer: Is it that simple?

Dr. Goulston: It's that simple. But there's also PrEP, which is pre-exposure prophylaxis, which is with a medication that they can take called TRUVADA, and that helps prevent cases in people who engage in higher risk behaviors.

Interviewer: I've seen down at the Pride Center and stuff, there's posters and stuff about PrEP. What is PrEP exactly? How does it prevent? It sounds like it's a full blown vaccine, but . . .

Dr. Goulston: No. It's a medication that you have to take every day and it prevents you from getting HIV if you engage in sex or exchange blood with someone who has HIV.

Interviewer: Now, is it expensive?

Dr. Goulston: It's extremely expensive. It's about $1,700 a month.

Interviewer: Wow, and is that just because it's new? Is that because . . .

Dr. Goulston: No. That's the cost. It's not new.

Interviewer: So it might be a little easier to just . . .

Dr. Goulston: It's part of the cocktail that we give patients when they have HIV.

Interviewer: It's the same cocktail that you give after the infection, but it helps prevent it?

Dr. Goulston: Correct.

Interviewer: What are some of the side effects of PrEP?

Dr. Goulston: First, you have to have to not be HIV positive to begin with. We screen patients for that. It can also treat hepatitis B, which is one of the good things about it. But as far as side effects, it can cause renal toxicity which is kidneys, and it can also cause osteoporosis or thinning of the bones.

Interviewer: Are those side effects pretty common? Are those . . .

Dr. Goulston: The thinning of the bones takes a while and the kidney dysfunction can occur in not the majority, but in some patients it can occur.

Interviewer: This isn't necessarily . . . It's not 100% prevention?

Dr. Goulston: No.

Interviewer: What are the rates of prevention?

Dr. Goulston: It's supposed to be helpful in up to 90% if you take it. But if you don't take it, it doesn't work, number one. Then if you have someone who has a more resistant virus and they are the person who's infecting you, there has been one case of transmission in someone who is taking PrEP and was documented to actually be taking it at the time that they were infected, but they got it from someone who had a resistant virus.

Interviewer: What kind of patient is PrEP good for?

Dr. Goulston: Anyone who has multiple partners. It would be a good person or someone who is monogamous with a partner who is HIV infected, that would be a good one, or someone who is in a partnership and they want to get pregnant, and one of the couple is positive and the other one is negative.

Interviewer: After talking about prevention and PrEP, if there is someone who is wondering about it or might be engaging in some of these behaviors that might expose them to HIV, what is the one take-away message you would have for them?

Dr. Goulston: That PrEP is effective and it can reduce the risk for HIV by at least 90%, and that they should come in if they're so interested, and we can help them.

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Interviewer: It wasn't too long ago that HIV treatments were a nightmare and the diagnosis was a death sentence. What's treatment like today for HIV positive patients?

We're here with Dr. Adam Spivak. He's an assistant professor in the School of Medicine and he specializes in HIV. And today we're talking about some of the HIV treatments available these days. How is the treatment today different than say what we did 10 years ago, 20 years ago? How has treatment changed?

HIV Treatment and Care Has Changed in Recent Years

Dr. Spivak: I think one of the things we've come to recognize is that the real revolution in HIV care began roughly in the mid '90s, by 1995, '96, with the introduction of combination antiretroviral therapy and you go back to the medical journals and recognize from the scientific studies how miraculous that was. Taking a disease that for the previous 15 years, from its first descriptions of AIDS in 1981 through, again, the mid '90s, this was a death sentence for patients. This was a disease that we really could slow down but not stop and that was killing more and more people every year. And we got these amazing combinations of drugs and people started to do fabulously well.

However, that didn't seem to apply to everybody and even though the drugs were so great, it was really under the rubric of a controlled medical study that we were seeing the benefits. And so, when you bring those into the real world and you're asking people to take at least in those days, difficult combinations of medicines that had lots of side effects, had to be taken every day, some with food, some without, some refrigerated, some not, it was extremely difficult to do. Even the most compliant patients, any of us trying to take medicine three times a day, it's difficult. And to ask people to do that up to 20 pills, it was really, really hard.

So I think what happened in the late '90s, early 2000s, was the recognition that we needed to do more than just sort of have the medicines available. And a physician just writing a prescription is not enough, which is perhaps an obvious thing in retrospect. But a clinic like ours is trying to really maximize the benefits of these medicines by providing enough of the resources to actually make it happen.

Interviewer: So specifically with medicines, what has changed? Are we still dealing with those 20 pills a day, 3, 4 times a day or what are they dealing with now?

Dr. Spivak: Yeah, luckily that has also changed and so that's really perhaps what we would call version 1.0 and that's way actually, luckily in our distant past. What has happened in the last certainly 10 years or so, is that we've gotten some new medicines and what the drug companies have also provided, are combination pills. So we have some new classes but also a recognition that those early days, medicines are only good if you can take them, you can tolerate them. And we are now to the point where we have four or five first-line regimens that are one pill, once a day.

Within that pill are three different medicines. They're co-formulated, minimal side effects. Again, very easy to take. Take on an empty stomach, take them with food, really not a huge deal. And this has really freed people to live their lives and take these medicines on a regular basis, without missing them, and basically live long healthy lives.

What to Expect at an HIV/AIDS Clinic

Interviewer: Besides the medications, just the straight up treatment. Take me through. An individual has tested positive for HIV and they come into your clinic. What do they expect when they come to the clinic there?

Dr. Spivak: HIV, even though the picture I was just painting, had been a life-threatening, devastating illness, and is now essentially a chronic medical condition that can be well controlled with medications, it's a disease with a lot of stigma. And so it's a devastating diagnosis to have, it is an extremely difficult thing for patients who are newly diagnosed.

So my first visits, and I know this is the same with my colleagues in the clinic, when I sit down with a patient who is new to the clinic and new to the diagnosis of HIV, we essentially spend the first visit or sometimes first several visits, just talking it through. Just talking about what it means. A lot of reassurance. A lot of education trying to get the patient up to speed with modern treatments, with life expectancy, with how they acquired HIV.

There's often a lot of discussion, a lot of reflection about what happened, what risks were taken, what can be changed going forward. I think I'm an optimistic person at baseline, but there's a lot to be optimistic about in this illness. And I think one of the messages I try to get across is that, "You're going to be okay. You're going to be fine. This is a partnership. We have phenomenal treatment. You're going to live a long healthy life."

And again, perhaps on the on the bright side or the silver lining, any number of patients that will come back after six, nine months, a year, obviously we have been seeing each other in clinic in the interim but they'll come back and reflect upon those first visits and they'll tell me how much they've changed.

A lot of the changes that they identify in their life after a diagnosis of HIV are positive changes. Some of the behaviors that may have put them at risk in the first place leading to their diagnosis have changed. Their lifestyles have changed and so I think certainly if people could go back and reduce those risks and minimize their chances of HIV diagnosis, they would.

But I see this a lot where people come in and realize that this in some ways was a wake-up call and they're leading a healthier, happier life than they were, believe it or not. So it's not necessarily something we tried out right away, but there can be some positive benefits. So it's a lot of talking. We take it slow at first.

Interviewer: So if there was one thing with the new treatments, with the clinic care and everything, that you would tell to someone who had just found out that they were HIV positive, what would it be?

Dr. Spivak: I would say what I tell my new patients, which is, "You're going to be okay. We're going to take care of you. You're going to live a long, healthy, productive life and you're entering a new phase of that life with a new set of partners who's going to help you through."

updated: December 1, 2022
originally published: February 22, 2017

Interviewer: Misconceptions and misunderstandings about HIV AIDS up next on The Scope.

Announcer: Health tips, medical news, research and more for a happier healthier life, from University of Utah Health Sciences, this is The Scope.

Interviewer: So we're here with Dr. Adam Spivak. He is an assistant professor in the School of Medicine and a specialist in HIV. What we're talking about today is some of the misconceptions. Even in 2016 we've learned so much about the virus and what it means, but some of these misconceptions still are out there. So, let's go ahead and cover some of these. What about transmission? Like, can you get HIV from kissing another person or touching them or sitting on a toilet seat or some of those old kind of . . .

Dr. Spivak: HIV is transmitted primarily sexually, and it can also be transmitted through blood. It cannot be transmitted through saliva, through casual contact, sharing a toilet seat in a public bathroom, sharing food with someone who is HIV infected. None of these are at all put anybody at risk.

Interviewer: But those stigmas did exist once, right? Because they must've come from somewhere.

Dr. Spivak: Oh absolutely, absolutely, and of course in the early days when AIDS was first described in the early 1980s we didn't actually even know what caused it. It took two years. It was not until 1983 that a novel retrovirus, HIV, was discovered as the cause of AIDS. So you can imagine a disease that was causing such severe illness and deaths and you don't know what causes it. We didn't even know entirely that it was an infection for those first few years that a lot of stigma, a lot of stories circulate, and certainly those are powerful and have a way to persist.

Interviewer: One of the other misconceptions at least historically that might still kind of linger on today is you just see some of these old news clippings or these old photographs and things like that where people are referring to HIV and AIDS as a gay disease, as a gay cancer or something like that. We're starting to find out that that's not true.

Dr. Spivak: Yeah, no, no, no. Worldwide HIV is transmitted sexually actually through heterosexual sex as the predominant form of HIV transmission. In the early days again populations that seemed to be hardest hit were gay men, men who have sex with men, injection drug users, sex workers, and interestingly enough people of Haitian descent. But again, that has persisted along with the recognition of the early spread of AIDS among gay men as this population to be shunned. Of course when we're talking about the 1980s we're talking about a group that was very much discriminated against that felt very marginalized. Unfortunately a new disease, a lethal disease, a disease of unknown origin that seemed to be spreading like wildfire had the effect of amplifying a lot of those frankly prejudices that were already present in society.

Interviewer: What about HIV positive women who might be worried about whether or not they can ever have kids or be pregnant? What are some of the misconceptions about that?

Dr. Spivak: One of the real highlights, one of the bright spots with regard to prevention of HIV transmission is mother to child transmission. What we have learned through a number of really well done studies and now many years of clinical practice is that pregnant women with HIV who are started on anti-retroviral therapy on the treatment for HIV really do not pass on HIV to their infants. We know that even a single dose of the medicines given at the time of delivery can reduce transmission from mother to child. It appears as best we understand it that HIV transmits at the time of delivery. Even just a dose or two doses of the medicine at that time is a very powerful preventative. We go a few steps further than that and get mom fully treated, and in those circumstances transmission from mother to child is almost unheard of in the United States and Europe where we do this on a regular basis today, so a real bright spot in terms of HIV prevention.

Interviewer: What about some of the ideas and maybe stigmas that the disease is a death sentence, that if you catch it your life's over?

Dr. Spivak: When AIDS was first described in the 1980s up until the mid-1990s, we did not have reliable treatment and this often was a cause of death in folks that were otherwise young and healthy and in the prime of their lives. The stigma, the stereotype, the concept that HIV AIDS is a death sentence certainly has its roots in truth. However, it's 2016. Starting in the mid-1990s as we've discussed, 1995, '96, the introduction of what we call combination anti-retroviral therapy, new drugs hit the market. It's still what we use today. These are fabulous treatments for HIV. Our patients are living long healthy lives. They have to take the medicines every day.

Untreated absolutely it is devastating to the immune system. It leads to what we call opportunistic infections and ultimately to death. We saw that very graphically in the first decade and a half of this illness. However, what we see today with patients that are able to come in to our clinic, get access to care, take their medicines on a regular basis is that they are leading long, healthy, productive lives and are doing fabulously well.

Interviewer: What's one of the top things that you would suggest for people to have done on this World AIDS Day?

Dr. Spivak: Oh absolutely I think the most important thing that people can do is get tested. I say that because the vast majority of the United States population has never had an HIV test. Now most people may not be actively at risk for HIV which is to say they're not practicing unsafe sex, they may not be injecting drugs, but we do know and there've been a number of studies that have shown that there are quite a number of people living today who have HIV who are not diagnosed. That's a tragedy on a number of fronts. We've talked about the ability to get these folks treated. It ultimately will affect their health. They're also at great risk of spreading the disease.

So, I think the test we have for HIV is one of the best diagnostic tests in modern medicine. It's incredibly accurate. A negative test in the setting of someone who's not at risk for HIV is very reassuring. It sits on their medical chart and they never need to get tested again. We're trying to get most people from zero to one to get tested. Of course the few folks who may have been at risk in the past or still practicing high risk behaviors with regard to HIV, and we're able to identify them and diagnose them with HIV, we're really going to be able to not only help them but help potentially partners help them from spreading the disease.

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Interviewer: Traditional medicines that interfere with life saving AIDS treatments, up next on The Scope.

Announcer: Examining the latest research and telling you about the latest breakthroughs. The Science and Research Show is on The Scope.

Interviewer: For the 35 million people worldwide who are living with AIDS, antiretroviral therapies are life saving medicines that can slow or halt the disease. But in some non-western countries, cultures can impact the effectiveness of treatment.
I'm talking with Dr. Lou Barrows, professor of pharmacology and toxicology at the University of Utah. He's investigating interactions between traditional medicines and antiretroviral therapies in Papua New Guinea. Dr. Barrows, how much of a problem is AIDS in Papua New Guinea? Why did you focus on that problem?

Dr. Barrows: Well, Papua New Guinea is an interesting case, it has, it's the only country in the South Pacific with and established HIV epidemic, but it's fairly low level. It's less than 1% nationwide, but in some villages the incidents of HIV is around 10%, and so it's of great concern that it still might spread.

Interviewer: So maybe you can talk a little about traditional medicines in Papua New Guinea, and how much that is a part of their lifestyle there.

Dr. Barrows: It's generally accepted that Papua New Guinea is like many of the developing countries in the world where about 80%of the people use medicinal plants for health purposes, and it's certainly part of the culture. And so we had some, quite a bit of background data on commonly used medicinal plants in Papua New Guinea, and some understanding that a lot of people use them a lot. And that when people are being treated with western medicine they go home and they also take their vitamins, their nutritional supplements or their herbal medicines, whatever you want to call it.
So, it's clear that there is potential for these things to interact, and there is lots of data from western medicine showing interactions of dietary supplements and medicines. So it was a logical question to ask.

Interviewer: And so what did you find?

Dr. Barrows: The approach we took, basically some in vitro assays looking at the ability of one drug to interfere with the activity of another, either by interfering with its metabolism, interfering with your body's ability to get rid of it, or by inducing enzymes that allow your body to get rid of things faster. And so, obviously if your drinking grapefruit juice and it inhibits liver cytochrome P450 3A4, then drugs that are metabolized by 3A4 are going to be at higher levels in your body and they might actually reach toxic concentrations, and this has happened.
That's the same system, identical system we use. But instead of things you might find at our grocery store, we use, we had our list of the hundred most used medicinal plants in Papua New Guinea from the database and so we went and collected them and looked at their ability to interfere with drug metabolism.

Interviewer: So when you see this enzyme, the cytochrome, when you see it go up, the activity go up.

Dr. Barrows: So if the enzyme goes up, then it's more effective at clearing the drug from your body. So then the drug might not reach effective levels and this has also been shown to happen.

Interviewer: So you found that some extracts from some traditional medicines actually raised the levels of the cytochrome and some lowered them. Are you talking about big effects or is it enough to suggest that it might, in some cases, totally inhibit the effects of the antiretroviral therapy or can you make those sorts of conclusions?

Dr. Barrows: I think we can because there's enough experience in drug development in western countries with big pharma and my colleagues here have actually been working in that capacity. So they have the same standards for what's considered a predictor of a clinically relevant effect.

Interviewer: What do you intend to do with the information you have now?

Dr. Barrows: I'm actually also an adjunct professor at the University of Papua New Guinea. So my colleagues at UPNG are quite interested at making sure this information gets back to the national AIDS council, well it actually already has. And they and the national AIDS council are now keen at putting together basically a little pamphlet that will go around to the AIDS clinics just identifying the different plants in the local languages. Papua New Guinea is an interesting place because there's supposedly over 800 different language groups, it's very diverse.

Interviewer: Barrier number one.

Dr. Barrows: Right, so it'll be a long pamphlet. Basically some of the most, what we think are the most problematic ones, the patients coming in for their antiretroviral therapy can be counseled to avoid consumption of this while you're taking these drugs.

Interviewer: What are the chances of that working? I mean, you're going against hundreds of years of culture, right?

Dr. Barrows: You know, its funny, I'm sure there will be a whole spectrum depending on the person and the village and how much they believe, how much they believe or they don't believe the health care workers or whatever. Most of the people I've met out in the bush, they're all pretty independent thinkers and if they understand the issue, then they're going to the make the logical decision. And if they understand that you take this at the same time you're taking this, this won't work, then they'll follow it.

Interviewer: Does your research have any implications for us here in the United States?

Dr. Barrows: So, one issue for us here in the U.S. is that while these plants are commonly used in Papua New Guinea, they are not kind of the golden seal or the cranberry juice or the Echinacea that are the major products in the U.S. But there is kind of a shift in these dietary supplements available in the U.S. and that's because of this global access to everything over the internet.
You can now buy many of these plants that we thought were Papua New Guinea traditional medicines, you can buy them over the internet for all sorts of purported uses, whether they are active or not I don't know, but some of them are pretty active at effecting drug metabolisms.

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Host: Aids is one of the most significant public health challenges worldwide. My guest, Dr. Sundquist researches how HIV infects the body, with the goal of finding ways to stop it. His outstanding research contributions recently earned him a seat on the prestigious National Academy of Sciences.
You investigate how the human immunodeficiency virus, HIV, the retrovirus that causes AIDS infects people?

Dr. Sundquist: Yes, the thing we're most interested in right now is how the virus interacts with the host cells that it infects. So viruses are fairly simple replicating machines. In the case of HIV they only make 12 proteins and that's as compared to 20,000 proteins that a human cell would make. And so one of the interesting aspects of viruses is that they have to use host cell machineries and pathways to replicate and that's something that interests us.

Interviewer: Why does that interest you? What do you hope to gain by learning that information?

Dr. Sundquist: I guess there are a series of reasons to do it. One is a simple curiosity, I think; understanding the world around us is a valuable goal. But of course we would expect that understanding leads to important spin-offs. And two, areas where one can envision such spin-offs and that have been realized in a number of cases, one is in therapy, so of course HIV is still a very important biomedical research problem. There are literally more than 20 million people who are HIV positive worldwide and so that's a huge health problem, and drug resistance is an increasing problem. And so we need to understand new vulnerabilities of the virus and we can only do that by understanding how the virus replicates.
But maybe a less obvious but still very important aspect of this type of work is that we can learn a lot of cell biology as well. So viruses, because they use host cells pathways, are actually the ultimate cell biologists, and so if we follow them we can learn a lot about cells work. And that's been famously, for example, oncogenes, which are the genes that go awry when people get cancer were discovered by studying retroviruses and understanding how they transform cells. And so this is something that keeps happening again and again is that we study a good model system and make fundamental discoveries that have impacts in other areas that we couldn't have predicted.

Interviewer: So can you talk about one area of your research, what are you focusing on?

Dr. Sundquist: Sure, one of the things we work on fairly intensively is understanding how the virus exits cells. So if a cell is infected in order to spread the infection the virus has to leave that cell. And we're interested in how that happens. And we got interested in that in a collaboration initially with Myriad Genetics where we were able to show that by a tech company here in Salt Lake City. And together we were able to show that the virus uses a host cell pathway called the escort pathway to leave cells. And the interesting spin-off, that was just over a decade ago, the interesting spin-offs are that we now understand that almost all envelope viruses use the same pathway to leave cells, so this has turned out to have quite a global impact on our understanding of viruses in general.
But the other thing that's happened is that this pathway, which of course performs important cellular functions, the cell isn't making these proteins so they can be infected by viruses, but rather to do other things. It turns out that the most important function of this pathway we now think is in the final step of cell division. And so a lot of what we do now is study how cells divide, rather than how viruses leave cells, even though we got into the problem through our interest in viruses.

Interviewer: Okay, so the escort pathway actually is something that occurs in human cells, but the virus needs it to get out of the human cell so it can infect other cells; is that right?

Dr. Sundquist: That's exactly right.

Interviewer: Okay.

Dr. Sundquist: And that's fairly common; as I said HIV and other simple viruses have only a dozen genes and so they have to use host cell pathways and reprogram them in order to do many of the steps of viral replication.

Interviewer: Why do you think this work is so fascinating? I mean, you've been studying HIV biology...

Dr. Sundquist: Why can't we quit?

Interviewer: Exactly. Is it an addiction?

Dr. Sundquist: Yeah, it is a little bit of an addiction. I think that you have on the best days, and they don't happen very often, you have a feeling that you're seeing something you and your students and your post-docs are seeing things that nobody has ever seen before, and understanding things that nobody has ever understood before. And that's sort of an exhilarating feeling, and it doesn't happen so often. Much of what we do is quite routine, but I think the idea that you can discover something that hasn't been known before is quite exhilarating.

Interviewer: What are you most excited about right now, in looking at that...?

Dr. Sundquist: The thing that I'm most excited about right now? There's are a subset of machinery of the escort pathway that we think forms filament strings basically and that those strings act like a noose from inside the neck of a budding virus and pinch the membrane together so the virus can leave. And they seem to do the exact same thing when cells divide. So they sit at the region between the two dividing cells and pull the membranes together. And we have a very talented young faculty member in our department, Adam Frost, and together with Adam Frost our lab and people in our lab have been able to I think make real progress in understanding the structure of those filaments. That's quite recent; we haven't yet published that. And it gives us at least ideas about how the noose might work.

Interviewer: I know Adam Frost has come up with these really cool visualization methods for these machines and cells. Have you been able to see a picture of this noose?

Dr. Sundquist: Yeah, we have at least what we think is the first picture of what it looks like. And I should say that we have a long-time collaboration with another structural biologist, Chris Hill, who is also in the Department of Biochemistry. And between the two of them they've given us a huge number of pictures of how the escort machinery works.

Interviewer: It sounds like cliche, but a picture is worth a thousand words, right?

Dr. Sundquist: It is.

Interviewer: But what can looking at a picture of that structure do for you?

Dr. Sundquist: Yes, I think if you view this in analogy let's say to a car, you have no idea of how an engine works until you look at an engine and see what it's parts look like and how they all fit together. And that still doesn't tell you how it works. But it means that now you have ways of thinking about it in concrete terms, what a piston might do, and so forth. So I'm a big believer in structural biology and other ways of actually seeing what things look like. I think that often gives you clues about how they work.

Interviewer: You seem to not be afraid to collaborate with people who do different types of research than you do. Would say that's a fair assessment?

Dr. Sundquist: I hope that's a fair assessment. I think that one of the really fun aspects of science is that you have interesting bright people who are doing different but complementary kinds of things, and some of the most exciting science gets done when they get together.

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Interviewer: What exactly is rheumatology? We'll examine that next on The Scope.

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Interviewer: Dr. Tracy Frech is a rheumatologist at the University of Utah. What is a rheumatologist?

Dr. Tracy Frech: So a rheumatologist is a doctor that specializes in autoimmune diseases. Your immune system is a good system if it's fighting off infections, or patrolling the bodies for cancers. If it's attacking cells for no good reason and multiple organs, primarily the joints, then a rheumatologist can help determine how to best suppress the immune system so that doesn't happen.

Interviewer: So would a rheumatologist be involved in HIV and AIDS?

Dr. Tracy Frech: Fantastic question. No, those would be infectious disease doctors specializing because in that case your immune system is not functioning because of a virus.

Interviewer: Okay.

Dr. Tracy Frech: In autoimmune diseases, the etiology for why the immune system is not functioning is really not clear and so the way that you would treat an autoimmune disease would be to suppress the immune system, whereas in HIV an infectious disease doctor would give treatments to rid the body of the virus.

Interviewer: What are some examples of autoimmune disease that you would look at?

Dr. Tracy Frech: So examples of autoimmune disease can include Rheumatoid arthritis, that's 1% of the population, that's an inflammatory disease of the joint. Systemic lupus erythematosus or SLE, lupus can involve the kidneys and in that case a rheumatologist would work closely with a nephrologist, but also involves the skin, the joints, seizures can be seen, fluid around the heart and lungs, abnormal clotting and problems with the blood count. Systemic sclerosis or scleroderma is something that I myself specialize in and in this condition the immune system doesn't like the small blood vessels of the body and we work to improve both blood flow and modulation of the immune system's response to that poor blood flow.

Interviewer: So I might be a little bit behind here, but it sounds like you specialize in the immune system attacking the body.

Dr. Tracy Frech: Exactly.

Interviewer: How does the body get the point where it doesn't like itself? And it starts attacking itself? How does that happen?

Dr. Tracy Frech: So that's the million dollar question and there's a lot of interest. Is it because we're having more genetically modified foods, is it environmental pollution, why are we seeing more and more autoimmune disease nowadays then we did several years ago? And better understanding the immune system is actually a real interest in the University of Utah, better phenotyping or understanding that clinical presentation and how that ties into molecular medicine is really a push of our division and our interest of how we move forward in the future.

Interviewer: Is there a thought out there that's kind of the thought as of right now?

Dr. Tracy Frech: It's probably multifactorial, so you're born with genetics and how those interact with the environment is probably the critical question. It's a better understanding of the genetic background and those environmental triggers is really the forefront of how we're trying to understand these conditions.

Interviewer: Is it kind of comparable to a switch getting flipped?

Dr. Tracy Frech: So exactly. So why your immune system at one point in time does a really good job fighting off infections and then fights self is an important part of understanding these conditions. Lots of interest in molecular mimicry, meaning did a bug look a lot like self or modify self and so now after you clear the infection, is your immune system now recognizing self as foreign, there's interest in that. Lots of cool theories, particular interest in things like microcrymerism, is the mother pregnant with a child, her subsequent child cells from the first sibling somehow cross the placenta, get into the other child and now that's a little bit like self but not quite, and your immune system is triggered.
Lots of different theories on why your immune system suddenly decides not to act right and lots of really active interest in trying to understand, how as rheumatologists we can better understand these conditions. Whether it's not the same trigger in all individuals, yet all individuals look the same when they present with the disease, is one of the pushes for sort of better defining the molecular basis to disease and again, an interest of the University of Utah.

Interviewer: So it sounds like the immune system goes out and it goes, oh, this is bad, now I'm going to make a little note of what this looks like so if I ever see it again, so it's constantly being programmed.

Dr. Tracy Frech: Exactly, it's constantly being programmed and it has a great ability to diversify and be able to recognize similarities between viruses and bacteria and whether ourselves get in the middle of that, that's a lot of active interest in trying to better understand that.

Interviewer: Is there a, kind of a generalized symptom somebody might have if their immune system is starting to attack themselves?

Dr. Tracy Frech: So what we generally as rheumatologists take great interest in is inflammatory joint disease, so a joint that's red hot and swollen, that is not normal.

Interviewer: Okay.

Dr. Tracy Frech: So you know lot of people ache and a lot of people are fatigued and that can be a symptom of rheumatic disease, the important one is that red hot swollen joint and that's not something that rheumatologists really like to see because, again, not only define our profession early on but allows us to engage in a cost effective workup.

Interviewer: Does a patient need to go to their primary care physician before they can see you, or if they feel that something is very familiar in this conversation that we had, can they come straight to you?

Dr. Tracy Frech: So unfortunately we actually do require referrals from primary care physicians and the main reason being is fatigue and achiness is so common in the community and rheumatologists are so few that we actually do like the primary care provider to say, oh yes that is a red hot swollen joint and then they would call and get the patient right in, if the wait list was long they would call the fellow on call to get any patient with a red hot swollen joint in expeditiously so we could move forward.

Interviewer: What's the thing that really excites you about what you do? What do you love about it so much?

Dr. Tracy Frech: We make people feel better, so there's nothing better than to have someone come in and be able to really affect their quality of life by getting inflammation under control.

Interviewer: Is there something that you would like a listener to know or take away from this discussion.

Dr. Tracy Frech: Again, rheumatoid arthritis is 1% of the population and young, female, we like to catch early and make sure we prevent joint destruction or disease progression.

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