As an infectious disease specialist, whose research focus is HIV maternal child health, Jennifer Jao, MD, MPH, splits her time between sub-Saharan Africa and Chicago, investigating the long-term metabolic effects of in utero exposure to HIV and antiretroviral medications. In this episode, Jao retraces her path to global health and infectious diseases, and offers a deeper understanding of the complexities surrounding HIV/AIDS and the ongoing efforts to improve care and prevention strategies in women and children.

Guest: Jennifer Jao, MD, MPH, Attending Physician, Infectious Disease; Susan B. DePree Founders' Board Professorship in Pediatric, Adolescent and Maternal HIV Infection, Ann & Robert H. Lurie Children's Hospital of Chicago; Professor of Pediatrics (Infectious Diseases), Northwestern University Feinberg School of Medicine

Host: Patrick C. Seed, MD, PhD, FIDSA, Attending Physician, Infectious Disease; President & Chief Research Officer, Stanley Manne Children’s Research Institute; Children’s Research Fund Chair in Basic Science; Professor of Pediatrics (Infectious Disease) and Microbiology-Immunology, Northwestern University Feinberg School of Medicine

Listen on your favorite streaming platform:

Show Notes

Jao's work investigates whether in utero exposure to HIV could reprogram a fetus's metabolic and immunologic health, or could cause potential neurologic, developmental, and cognitive complications in longer-term health outcomes.

Although some of her work is conducted here in the United States, Jao's research is predominantly conducted in sub-Saharan Africa where 90% of the world’s HIV population resides. Her NIH cohorts are currently located in South Africa and Botswana, where around a third of pregnant women are HIV positive.

Earlier in her career path, Jao was motivated by the immediacy of providing direct care to individuals. While she ultimately took a more academic path, Jao sees her research as another form of care since research has the potential to impact larger healthcare systems and policy changes.

Starting out as a student of French literature, Jao utilized her language skills to study in Francophone speaking Africa. This exposure later shaped her decision to incorporate global health into her medical career, eventually leading to a specialty in infectious diseases.

Jao serves as a principal investigator for the Pediatric HIV/AIDS Cohort Study (PHACS), which offers vital insights through observational studies of perinatally contracted HIV in children and young adults as well as in HIV in pregnant women and their offspring. The study's results have been reassuring and suggest antiretrovirals in pregnancy pose no significant concerns, but also underscore the importance of long-term monitoring for potential issues such as weight gain and cardiovascular risks.

In the late 1980s, there was a 30% risk of mother-to-child HIV transmission without antiretrovirals or other HIV medications. Today, women with HIV who take antiretroviral medication during pregnancy can reduce the risk of transmitting HIV to their babies to less than 1%. However, even if a cure for HIV were miraculously found today, the complications of in utero exposure to HIV would still persist another 70 to 80 years potentially, in light of the current generation still impacted by mother-to-child exposure. This point emphasizes the long-term impact of such early life interventions.

Jao speculates that infrastructure issues are likely to blame for not being able to achieve total elimination of perinatal transmission, and healthcare infrastructures vary dramatically across the globe. She asserts that the Global North should be open to learning from other healthcare models in the Global South and avoid assuming superiority in healthcare, or worse, a form of contemporary “academic colonialism” in global health research.

Read the Transcript

[00:00:00] Pat Seed, MD, PhD: This is In Pursuit, research perspectives from Ann and Robert H. Lurie Children's Hospital of Chicago. I am your host, Dr. Patrick Seed, President and Chief Research Officer of Stanley Manne Children's Research Institute, one of the nation's largest freestanding pediatric research centers. All right, so let's get into it. We have a really special guest with us today, Dr. Jennifer Jao. Dr. Jao is a professor at Northwestern University of Feinberg School of Medicine, and she's an attending physician at Ann and Robert H. Lurie Children's Hospital of Chicago. She specializes in both adult and pediatric infectious diseases. Jennifer's research, as we're going to hear more about, is really broad and impactful, focusing on HIV/AIDS, maternal child HIV, pregnancy, metabolic complications of HIV and its treatment, and a number of different aspects around women's and pediatric health. She leads multiple NIH funded pediatric and maternal pediatric HIV cohort studies in both US and Africa, and she studies the long-term effects of HIV and antiretroviral therapy. So welcome Jennifer, to today's podcast.[00:01:12] Jennifer Jao, MD, MPH: Thanks for having me, Pat.

[00:01:14] Pat Seed, MD, PhD: Absolutely. So let me start with this because I always think it's best to hear from you how you think of your science. So you're at  a big family event. How do you tell people there what your scholarly work and your science is all about?

[00:01:28] Jennifer Jao, MD, MPH: You know, and I get asked that a lot. It depends on who I'm talking to, but if I'm talking to, let's say, a crowd of eager college students, I usually start by saying, I get to take care of women living with HIV and especially during their pregnancy, we try and figure out, if the medications that we give to pregnant women have any long-term complications or effects on those women and their children. And that sort of gets the ball rolling. And then they kind of ask, well, how do you do this? And then I kind of go, well, I get to travel a lot to do it too. And I get to do it here in the States.

[00:02:03] Pat Seed, MD, PhD: That leads me to actually a point that I think people outside of, particularly infectious diseases, but HIV work in general, are pretty surprised by which is, we think of current antiretrovirals, doing such a great job of, preventing HIV infection or managing it and things. And I think people get really surprised when they hear that being exposed to HIV in utero leads to some serious outcomes even if you're not infected. Can you just give us the big picture of what are the kinds of things that that early exposure that you just alluded to with, these amazing drugs that we have now. What does that alone lead to in the life trajectory?

[00:02:39] Jennifer Jao, MD, MPH: Yeah, so we talk a lot about perinatal origins of diseases and life course epidemiology. And I think it's that sort of extension of the Barker hypothesis, where we are wondering whether in utero exposure to an environment where there's an infectious agent, HIV, and a lot of inflammation that it's causing as well as the drugs that we have to give to quell that virus, does that whole milieu and that environment, when you're a fetus, mark you or reprogram your fetal metabolic health, and not just metabolic health, your immunologic health. My emphasis for research and complications of HIV and antiretrovirals is on metabolic complications, but there's a whole host, as you know, of immunologic complications, and just long-term, maybe even neurologic, not necessarily huge complications, but are there any developmental, cognitive, health outcomes that we need to watch out for the future. And so I think that's where the field is moving, when we talk about in utero or perinatally exposed children, who are uninfected, but were exposed in utero.

[00:03:52] Pat Seed, MD, PhD: Yeah, that's a great starting point. So of course we're gonna come back to that, but wanted to understand, one, where does your work happen right now? Where are you studying the problem of long-term, either the effects of in utero early life exposure to antiretrovirals or the kids who are infected and need long-term therapy to control HIV?

[00:04:11] Jennifer Jao, MD, MPH: You know, 90% of the world's pediatric HIV population lives in sub-Saharan Africa. So you gotta go where the people are. And that's where I go. Most of my NIH cohorts right now are in South Africa and Botswana, and that's where about a third of the pregnant population actually has HIV. I started my work earlier in Francophone Africa, and Cameroon, and Gabon, and Benin. But, as you may or may not know, the prevalence is just not quite as high, and I mean the HIV prevalence there. And so a lot of my work has moved towards South Africa, Zimbabwe, and Botswana. And of course in the US.

[00:04:51] Pat Seed, MD, PhD: What's your split of time? So how much time are you spending stateside and how much are you at study sites in sub-Saharan Africa?

[00:04:59] Jennifer Jao, MD, MPH: So I think early in my career, I spent significant chunks of time, like two to three months at a time, because you have to be the one to do the grunt work and it's you with the study team there. I'm blessed enough now where I've cultivated some really strong partnerships and I have collaborators overseas in Cape Town and in Gamberoni, Botswana who actually can run the operations and the logistics of a study so that I probably don't have to go and spend three to four months straight at a time, but certainly get over there at least two to three times a year for several weeks at a time.

[00:05:38] Pat Seed, MD, PhD: And I imagine, it's coordinating teams, but it's also each of those places probably have a lot of cultural aspects to conducting the work to partnering and all the things that are really important. Right? The secret sauce to getting good engagement with both research subjects and with patients, which sometimes the really cool thing, right, is that you're also probably providing care to some extent in addition to trying to understand the next level of care is through research.

[00:06:08] Jennifer Jao, MD, MPH: You know, you bring up a really good point when you said you're probably providing care. I think that's one of the key secret sauces, as you might say, is that if you're going to go overseas, and whether you have research in mind or not, you've gotta be prepared to learn and to give back and care for the very people that you are trying to evaluate and assess for research. And so that actually is how I started getting involved in global health. Not for the research, but actually, as someone who wanted to provide care. And I remember my first time when I went overseas, I was just a med student and that was, you know, my three or four month stint in Benin. But I was purely there to provide healthcare and it wasn't until I think my long circuitous route through med school and fellowship and whatnot, that I started thinking, gosh, research is really another way to provide care. It's one step removed, but it's a way to affect systems and policy change that's not just a one-on-one-on-one providing care. So it's really invigorating for me. I mean, I like the balance of it.

[00:07:16] Pat Seed, MD, PhD: Yeah, it definitely sounds like it. Actually, it's a great segue for me to go back to those early points and sort of think about what the journey was like and what some of the key pivots were for you, because I think your origins as a college student, right, you were a French literature major, so, I mean, it's gotta be quite a journey. So, so talk me through that. You mentioned that medical student experience. Where are the other points that sort of latched onto you to try and advance the care for the future of those same people that were part of your practice and your earlier engagement.?

[00:07:49] Jennifer Jao, MD, MPH: Most people ask me like, what do you have to do? What's your path? And I usually say, gosh, I wish I could tell you I had like a straight shot path. But, you're right, it started with me being a French Lit major. I actually wanted to be bio-political science and sort of do this whole pre-med shtick. And I realized I didn't like the biology as much as I liked French literature. So I spent a year studying abroad at the Sorbonne in Paris. And I still remember the last day of college thinking, what am I gonna do with this French Lit major? I wound up getting off a waitlist and going to med school, but it's kind of funny how the French literature major helped me in med school sort of decide, Hey, there's an opportunity to go overseas and wow, I should really go to Francophone speaking Africa because it's so, it's so hard, I think to get folks into Sub-Saharan Africa and non-English speaking parts. So that's how I decided to go to Benin because I already had the French. Fast forward a couple more years, obviously I went to residency and in residency, which I did at Rush University, I met Dr. Tina Schleisher, who is a longtime mentor of mine. And she had been friends with some folks in Gabon and she said, gosh, I know you wanna come and do research with me because she's a pediatric, peds intensivist, so she's a PICU physician. I wanted to do research under her in Nigeria where she was, and she said, but gosh, I really think with your French background you should go to Gabon 'cause I have just the right person for you. So, right. A lot of this is finding favor in the eyes of folks that somehow seemed to carve a path for you. It's not me figuring it out. So I did go to Gabon, spent I think about four to six weeks there in my last year of residency. And then when I finished residency, I sort of knew no matter what I do in medicine, I've gotta have some time to go overseas. So, I actually did general med-peds, internal medicine pediatrics, for a while and decided later to go into infectious diseases when we moved to New York. And so I did an MPH during my fellowship, and lo and behold, my first project, I thought, where am I gonna do my research? And I thought, I've gotta figure out something global health. And so I was able to dig back into some of my partnerships with folks at ICAP at Columbia who had placed me in Cameroon for a one month stint while I was still working as a general Med-Peds primary care physician and, reopened the door, wrote up a science project and that was my, fellowship, global health science project. And it was in HIV and then sort of the rest has been meandering through opening doors and research and such.

[00:10:41] Pat Seed, MD, PhD: The circuitous paths are so interesting, right? I'm sure that there's gonna be some other twists and turns along the way for you. Know you're part of the pediatric HIV/AIDS Cohort Study, PHACS, and co-chair the Nutrition Growth and Metabolic Working Group. Tell me a little bit more about that group. What do you do in that group and what are some of the really, what you find to be the most impactful things that have come from that group over the past five to ten years?

[00:11:08] Jennifer Jao, MD, MPH: PHACS or the Pediatric HIV/AIDS Cohort Study. I'm one of the multi PIs of that network, and I think PHACS is really the only network in the US that's been able to evaluate and investigate from an observational trial standpoint, right, because we have Impact who does a lot of the clinical trials, but from an observational study, we've been able to follow not only, children and now young adults who are born with HIV, so perinatally acquired HIV, but we've also been able to follow pregnant women with HIV and their children, some of them, we are following the cohort in their teens now, and that network is special because no other big network or cohort is looking at that in the US. Tons overseas, obviously, which I'm also a part of, but in the US that is the network that is doing the most amount of observational work, I think, in those two kinds of study populations and, you know, what have we been finding? I don't think we're seeing any terrible signals that say, oh my goodness, you can't use this drug in pregnancy, which is great. It's totally reassuring. Are we finding other, sort of, signals where we might wanna watch long term? Because it's one thing to say everything looks great in the first 12 months of a kid's life, but then, you know, is it gonna stay that way long term when they're 30 or 40? So you know, my stint is in the metabolic working group, and so we're really focused on things like weight gain, which is a big, sort of hot topic right now with the integrase inhibitors. Is there untoward weight gain in pregnancy? Is there untoward weight gain in our young adults with perinatally acquired HIV? Are there higher risks of cardiovascular disease and cardiometabolic poor outcomes in our kids who either were born with HIV or had that in utero exposure but are not infected. So I think those are the broad strokes of what we're looking at. Other working groups that are also looking at neuro development, and there's been quite a huge amount of work in that realm. I would say, again, I love the work that PHACS is doing because we've been able to sort of give some reassuring news. I mean, I would say reassuring news to the public that yes, as a pregnant woman, you can keep taking these antiretrovirals in pregnancy, which is a huge difference from what people were worried about when Cydiodine first came out, right, in the late 1980s. And people were very worried about whether or not there would be problems for the fetus. And so at least we can say there have been some good reassuring data.

[00:13:53] Pat Seed, MD, PhD: It's impressive to think that we're building on, or we now have the importance of looking at those long-term outcomes and effects, when not so long ago was all about just preventing transmission or getting infection or, even getting an infant through infancy into childhood and not developing aids and succumbing. It's a good point just to stop for a minute, and can you remind everyone that success that we're building on, what's the transmission rate for a woman who's treated in the US or in Botswana right now, right, who receives all the appropriate, pregnancy related medications, prevent transmission, and perhaps a little bit of dosing afterwards, to reduce the risk?

[00:14:37] Jennifer Jao, MD, MPH: In the late 1980s, there was a 30% risk of transmission. So one in three women would transmit HIV to their children without any kind of antiretrovirals or HIV medications. And now we've gotten it down to less than 1%.

[00:14:52] Pat Seed, MD, PhD: That's really phenomenal for us to be at that point. So that brings me to a big hairy question, which is right now, HIV is managing chronic problems, whether you're infected and we're managing it, right, as a child or you're uninfected, and these are, as you pointed out earlier, Jennifer, these are the consequences of changing those early life trajectories because of some of that exposure. Now here's the really, really hard question is, have you and your colleagues thought if we actually had a cure tomorrow, which let's just be really clear for everyone, that's not the case, what would be the tail of the chronic disease that we're thinking of because of the existing people who have been either exposed or they've had some chronic exposure to antiretrovirals as an example. What would be the overall burden? Are we looking at a tail of 50 years or is it a shorter tail? I'm just trying to help everyone understand the extent to which people have been exposed to these important medications, but the long-term consequences for us, really as a global community.

[00:15:56] Jennifer Jao, MD, MPH: I think that tail is as long as a kid who's born today is gonna live with HIV and that's 70, 80 years, you know, and so we owe it to those kids, if we had a cure tomorrow, every kid born today who's still gonna live for a long time, infected or uninfected. I think pediatric cure is at the forefront. A lot of us pediatricians in HIV have been thinking about: what do we need to do to inch us towards pediatric cure? But short of that and a vaccine, we are going to be dealing with the ramifications or questions of complications of in utero exposure for a good another 70, 80 years even if a cure were found today.

[00:16:39] Pat Seed, MD, PhD: Yeah, I mean, that's what I anticipated, , the point is that we're in this for a long time, right? we really need to keep the pedal down on the gas to keep moving forward and mitigating the chronic effects because just something's not coming in the near term to dramatically reduce that tail.

[00:16:55] Jennifer Jao, MD, MPH: I really think, why aren't we at elimination yet of maternal child transmission, right? I mean, that's been a hot topic and we've been kind of wondering, we have the tools to eliminate it. What is it that is preventing us? I mean, we've gotten it down to less than 1%, but why can't we get it to zero? I could offer a whole lot of reasons why, but that would be where I would love to see pediatric HIV go, towards really eliminating perinatal transmission, and not just here in the US, because already we still can't eliminate it in the US. But in sub-Saharan Africa, what do we need to do to get to elimination? I mean, I'd like to put myself out of a job, you know?

[00:17:37] Pat Seed, MD, PhD: Yeah. I mean, what are the top things that you'd attribute to us not being to elimination right now?

[00:17:44] Jennifer Jao, MD, MPH: I wonder if it is, one, we just don't have the infrastructure healthcare wise to do appropriate testing and getting women into care early enough, that's still a problem both in the US and in sub-Saharan Africa, parts of Southeast Asia. The drugs work, but they only work if you can get women into care. And then, on the backend, let's say you miss that chance to get the mother into care. Well, what do we need to do to strengthen our regimens in these babies who have either high risk of in utero infection or breast milk transmission. Do we need to be adding different things into our armamentarium: BNABS, broadly neutralizing antibodies, which we're all studying right now in the impact network, in addition to three, four drug, traditional antiretroviral regimens.

[00:18:38] Pat Seed, MD, PhD: Yeah, comforting to know that there's, at least from a therapeutic standpoint, there's a strategy, but I think the challenge, right, is that infrastructure part you talked about. It's investment and it goes beyond HIV, a lot of the infrastructure carries over to other ways that we support health and both preventative and treatment across the board. And it's different for every country too. it would be really egotistical for someone in the US to be able to tell the South African Ministry, oh, this is why you can't get to elimination, right? We can't even do it ourselves. So I really would love to see a lot more collaboration and sharing of what's worked and what's not. It's okay to say, Hey, we failed at this. Can we learn from another country? There's colonialism in the way that it was done 50, a hundred years ago. But there is this risk of academic colonialism that I struggle with every day in my global health work, right? And so how do we do the research that we need to do in, let's say, low and middle income countries, but also learn from them because they have a lot to teach us.

[00:19:42] Pat Seed, MD, PhD: We live in this very global city with a lot of diversity. I think there's perhaps a lot of ways to frame this idea of global is local and local as global thinking about the Chicago context.

[00:19:56] Jennifer Jao, MD, MPH: Absolutely. I mean, just from a micro level, half of the patient population and research population that I actually see in Chicago is made up of people from Sub-Saharan Africa or Southeast Asia or South America. So, I actually feel as though, even though I'm sitting here seeing patients in Chicago, I'm actually seeing Ethiopians, I'm seeing people from Gabon and Cameroon and Honduras and Ecuador, as well as African Americans in neighborhoods with significant health disparities. So it's the same problem. Health disparities, whether it's an international problem or a local problem, it's still at the core an issue of inequality. And how do we level the playing field? So I think obviously the contexts are different because we're in Chicago and we're in an urban setting or in the US. But there are core lessons to be learned when you take that same problem and you go overseas and say, well, why are there health disparities and why can't we get to 0% transmission rate? So I think of global, local, and those kinds of paradigms as well.

[00:21:07] Pat Seed, MD, PhD: Are there examples you can think of that you've seen abroad that you think that would really apply to Chicago and really benefit health here, even being in a different context?

[00:21:17] Jennifer Jao, MD, MPH: So two interesting things kind of dawned on me this year as I was doing research in Cape Town. My colleagues and I were doing some sleep studies and we all thought that if, we brought the folks in from X, Y, Z neighborhood that their sleep would be horrible because X, Y, Z. Right? So it's interesting because these participants were brought in, they had a sleep study done in the sleep lab, and they noticed that the sleep was impeccably good. And we all thought, what's up with that? Right? And it dawned on us later that actually those participants who came in said, this is the best night of sleep I've ever had because, a). I don't have guns going off, and b). I don't have to sleep with five other people in a small cramped space, and c). I don't think that anyone's gonna come and rob my house. And so I'm just giving this an example of the Oh yeah, I was so off the mark. And so one of the things I've learned about research and caring for patients by being overseas is you have to doubt yourself. I mean, not to the point that you're paralyzed and unable to function, but you have to always question, where did I come up with that hypothesis and that thinking? Because otherwise, you run the risk of just being a lone ranger and running and calling your shots, thinking that you're gonna go out to prove them. And you know, right, Pat, as a scientist, the last thing you wanna do is start interpreting your data so that it melds with what you have always thought and has been your opinion, but it's not what the data is saying. So that's one thing I've learned. I think another thing I've learned from a practical perspective is, we are very sub-compartmentalized and subspecialized in our healthcare system in the US, right? If you're an adult, you go to the internist. If you're a little kid, you go to the pediatrician. If you're, if you're pregnant, you go to the OBGYN. And so if I have a woman who has HIV and she's pregnant and she now has delivered and she has her child, she has to go back to her OBGYN to get her postnatal care. She has to go back to her potentially internist, who does HIV to get that care. And then she has to take her kid to the general pediatrician, but also maybe the HIV pediatrician to rule out HIV infection, and that's a lot of people that this poor dyad, mom and baby, have to go see. In Africa, they don't always do that, right? It's centralized. That mom and baby can go to one place and that kid will get tested for HIV, shots, general care. The mom will also get her HIV care and her obstetric care. And really, why can't we do that here? We started to do that and we've done that at Lurie's, right? We have a mom/baby clinic, but it's not that easy to implement that at every place in 50 states across the US.

[00:24:07] Pat Seed, MD, PhD: As we look forward, I think those are great examples, you know, around care models and ways to simplify things, particularly to get better engagement in healthcare, Which is ultimately what we can do to help keep people healthier. Well, thanks Jennifer. I really want to thank you for joining me for this podcast today. It's really been enlightening and I always so greatly enjoy the conversations we have.

[00:24:30] Jennifer Jao, MD,, MPH: Thanks for having me, Pat.

[00:24:31] Pat Seed, MD, PhD: For more information on Stanley Manny Children's Research Institute at Ann and Robert H. Lurie Children's Hospital of Chicago, visit our website, research. luriechildrens. org.