Dr. Daniels reviews the history of perinatal management, discusses the current recommendations for perinatal prophylaxis, and how to counsel parents who are breastfeeding and living with HIV.
Thank you so much for having me. I know many but not all of you. I'm Elizabeth Daniels, one of the PSID docs. I spend a lot of my time doing our HIV care, um, and I love this topic. Uh, preventing HIV transmission to babies is the best part of my job, um, and something that I'm always excited to talk about. I have no disclosures other than this is my family who have just sort of rewired my brain. Um this is my 2 year old, and I'm learning so much about how to be a better pediatrician now that I have a kid of my own. OK. So my objectives today are to introduce our perinatal HIV team to you guys. Um, we're always here, we're always happy to help, uh, talk a little bit about the history of perinatal HIV management, which is something that I really like, uh, and then talk about current perinatal prophylaxis regimens to prevent our babies from acquiring HIV. Uh, talk about breastfeeding or chest feeding, which is a really hot topic in perinatal HIV management, and then talk about the current state of our perinatal HIV prevention efforts in the US. And sorry for those on Zoom, I wanna look at the people in the room, so I'm not looking at my camera, that's why. So we have a really, really big team uh devoted to caring for people living with HIV, uh, people exposed to HIV in our region. Um, this side is not comprehensive at all, uh, but we have 3 physicians, um, myself, Doctor Melissahnne and Doctor Storch who see young people living with HIV and then a whole, whole team of nurse coordinators, nurse managers, case managers, pharmacists, um, caseworker, many more people that I can call out by name. Um, specifically on our perinatal team, there are a few names that I think that you should know. Sheena Blackwell is one of our health coaches. Deborah Colquitt is a perinatal case manager. Carrie Shuzy is a clinical nurse coordinator, and then Alex Meadows is another clinical nurse coordinator who's really now the point person for perinatal HIV care, and she just coordinates a lot of care for expecting parents, uh, and then for babies. There are lots of ways to reach us. You can always contact pediatric infectious diseases on call, um, but if we're already seeing a baby, maybe we're following an exposed baby in our clinic and you're the primary care pediatrician for that baby, uh, then Alex Meadows is gonna be a really good point person. Uh, if you're the primary care doctor for one of our children living with HIV, then Phyllis Ballard, who just won our nursing Excellence Award after decades, so much deserved, is an excellent point person, and then I'm always just super happy to chat. Um, again, I love this work. So, I think it's fun to start with cases. So I wanna start with a phone call, which is a phone call that I got when I was a PAD fellow, um, called by Children's Direct by a pediatric hospitalist out, uh, in a hospital in our network about a full-term 2 year old baby born to a mother living with HIV and the, uh, hospitalist asked me for management recommendations for this baby, do they need labs? Do they need meds? And also, by the way, mom is breastfeeding her baby right now. And that blew my mind, um, because at that point, we've been preaching for a long time, uh, that anyone living with HIV in an area with safe access to formula should not breastfeed their baby or some people prefer the language of chest feeding, uh, because of the risk of HIV transmission through infant feeding. Um, but that landscape is really rapidly changing, and that's something that I'll spend some time talking about today. So, here's some of the questions that I had. Hopefully, these are some of the same questions that go through your mind, um, but when I'm getting one of these calls from you guys, I want to know when the parent was diagnosed with HIV, uh, specifically, what I'm trying to figure out is, was the parent diagnosed with HIV before pregnancy or during pregnancy? Because during pregnancy, you have a high viral load, if you have acute HIV and that's the highest risk transmission, uh, scena. Scenario. I wanna know if the parent is on antiretrovirals. Hopefully, they are. We have a lot of resources in place to try to get people on antiretrovirals always, but especially during pregnancy. I wanna know what maternal viral loads were during pregnancy, whether there were any issues um with adherence, um, whether the parent has any antiretroviral resistance that might inform what medicines they're reaching for for the baby. I want to know what other infectious testing this parent has had, making sure, you know, with all of the congenital syphilis, uh, that we're seeing, that the parent has had recent testing for syphilis. Uh, we're increasingly seeing hepatitis C in people with childbirth. Potential, so I want to see hep C testing. And then lastly, like I talked about, this was the first call that I'd ever gotten about breastfeeding for somebody living with HIV, um, so I was thinking, is this even something that we're going to support? I promised a little bit of history, so here's our history for the day. Um, unfortunately, there have been nearly 10 million cases of perinatal HIV transmission globally since the beginning of the HIV epidemic, mostly in low resource settings, but certainly many cases here in the United States. These cases were reported starting as early as 1982, and at that time, interventions were incredibly limited, and some of my colleagues like Doctor Greg Sturch will talk about taking care of these babies as they're dying, uh, which I truly can't imagine. Uh, without intervention, the rate of perinatal HIV transmission is about 25%. Uh, interestingly, most of the transmission happens, uh, late in pregnancy and then during delivery, so only 20% of transmission happens before 36 weeks gestational age, then there's about 50% transmission between 36 weeks in delivery, and then another 30% during active labor and delivery, and then further transmission can occur due to infant feeding. In 1994, people got brave, and there's a really famous study on this PCG protocol, number 76, which is a landmark trial of zadobidine during pregnancy. They enrolled people living with HIV, not AIDS, with no prior treatment, and they gave expecting mothers a really onerous regimen of zadobidine 5 times a day. And if anyone knows something about zadobidine, you might know that this is hard to tolerate. And they gave IV zadovidine during labor and delivery, which is of course something that we still do. And then they gave the baby zadobidine syrup every 6 hours for 6 weeks, and this showed a really dramatic 67% reduction in mother to child transmission, a huge success, and this was the first child that showed that we can do something about this. After this, we really refined our approach to perinatal HIV transmission through uh universal maternal HIV screening, uh, antiretrovirals for both moms, and then prophylaxis for babies, C-sections for people with high viral loads at the time of delivery, and then, of course, we've been preaching avoidance of breastfeeding in research, resource-rich settings for a really long time. Uh, and we with this have had a dramatic, dramatic impact on transmission to our babies. So I love this figure showing that after the PACG study results were published, uh, with the STAR, perinatal HIV transmission just plummeted. We can prevent 99, 99.9% of perinatal HIV transmission events, so really exciting. So now that we know that we can prevent perinatal HIV transmission, the question that we're facing is how we can do this in like the least invasive, least toxic way possible. Nobody wants to give babies zoovidine any longer than necessary. Um, so our kind of questions have shifted from how do we prevent perinatal HIV transmission to how many medications do these babies really need? How much do we need to do here? And evidence has really mounted in favor of shorter regimens for infant prophylaxis. This has not been established, unfortunately in clinical trials, but other countries have had a lot of success with shorter zadobidine regimens for babies born to people who have a very low risk of HIV transmission, meaning they have had virologic suppression throughout pregnancy. So throughout the time. I've been doing this, which is not all that long. We've gone from 6 weeks for all babies to 4 weeks, and now for our lowest risk babies, we're doing as little as 2 weeks of prophylaxis. So a pretty big shift again, just in the time that I've been training. Uh, the UK has a similar approach, 2 weeks of zoobidine for babies meeting very low risk criteria. Uh, zoovidine is really myelosuppressive. So I've made a lot of babies anemic and I've made a lot of babies very neutropenic. Uh, and if you give them less zadobidine, you do less of that, which is great. And then Switzerland actually does no antiretrovirals at all for very low-risk infants. That's bold. We're not there, um, but they haven't had any perinatal transmission reported, so good for Switzerland. Um. I do want to be clear that some babies still require longer multi-drug regimens, uh, namely the babies who have parents who did not achieve neurologic suppression during pregnancy. So if you have a parent who has high viral loads during pregnancy, if they had acute HIV during pregnancy, we have evidence that a 6-week regimen of medications and we do a combination medication regimen is superior. So for those babies, we're still recommending 3-drug prophylaxis. These are the latest uh guidelines for antiretroviral management for infants with in utero or intrapartum HIV exposure. So first, we're looking at does the parent have a viral load greater than 50 after 20 weeks' gestation because we know that later in pregnancy is when the risk of transmission is higher. Um, and if no, then in most cases, not all, but in most cases, we're actually recommending just 2 weeks of zoovidine for babies, which is great. Uh, if a parent has a viral load higher than 50 copies after 20 weeks, then we're looking at was that right around the time of delivery, was that a little earlier and then making decisions, uh, for Babies whose parents had viremia right at the end of pregnancy, I'm still doing 6 weeks. For some of the babies whose parent might have been biremic around the 20-week mark and then suppressed, I might start with the 3-drug regimen and then de-escalate. Again, there are some special situations that impact risk. So again, acute HIV is something that I'm always on the lookout for, adherence concerns if babies are born very premature, although we don't have data to suggest that that is a higher risk scenario, and then of course infant feeding plans. OK. Any questions about perinatal HIV medication selection, kind of general management before I talk a little bit more about infant feeding? OK. My gosh, the room is so silent. Please talk to me. Um, so then getting to the kind of a hot topic in our clinic, which is breastfeeding. So before the availability of uh combined antiretroviral treatment, the risk of HIV transmission from breast or breast feeding was 16%. That's obviously way too high. Um, but what is the risk of transmission with modern antiretroviral therapy? Do you, if somebody has a consistently undetectable viral load during pregnancy, do you think that the risk of transmission through uh breastfeeding is still 16%? Do you think it's 10%, 5%, or less than 1%? Less than 1%, it is, but it's not zero, which is important. Uh, even if somebody is consistently virologically suppressed, the risk is not zero, but it is very low. So thoughts on breastfeeding for these infants um has really dramatically changed. Uh US national guidelines were updated uh January 2023, which is not all that long ago, to recommend supporting breast or chest feeding for people living with HIV. Under certain circumstances who are living in higher income countries, and this shift was really born out of a lot of patient advocacy. There's a wonderful group called the Well Project, uh, which is an advocacy group really focused on women living with HIV. This shift acknowledges benefits of breastfeeding, importance of individual choice, cultural considerations, equity, and overall reflects a broader shift towards more patient-centered decision-making in HIV care instead of us just telling people, here's exactly what you have to do. Um, and at the risk of kind of oversharing, this has It's just been an interesting time for me to be thinking about this work as I have a baby myself, making my own decisions about how I'm going to feed my baby, and that experience has really underscored for me how incredibly personal that decision is and how I don't want anyone else telling me how I can feed my own baby. Uh, so, What's really important here is good, good counseling beginning as early in pregnancy as possible. So people living with HIV who are interested in breastfeeding should be informed that replacement feeding with formula or donor milk, which of course is hard to access in the communities, eliminates the risk of postnatal HIV transmission. Achieving and maintaining viral suppression through antiretrovirals during pregnancy and postpartum decreases that transmission risk to less than 1%, but again, it's not zero. There have been multiple case reports of people who've been virologically suppressed who have transmitted HIV to their babies through breastfeeding. Um, people who are not on antiretrovirals or who have not. Uh, gotten their viral load suppressed for whatever reason can be hard, uh, are still strongly advised against breastfeeding. And I also try to be really clear with people that there could be situations where we would recommend stopping or modifying breastfeeding if somebody becomes viremic, for example. So ongoing monitoring is certainly needed. What to do with prophylaxis in this setting. Again, I know this isn't a decision that you guys are making, but you might be taking care of a lot of these babies from the primary care end. We really don't have great data that tells us what the best prophylaxis is for infants who are breastfeeding. Some people do as Little as 2 weeks of zidovidine. Some people do as much as 6 weeks of 2-drug therapy followed by ongoing extended prophylaxis throughout the entire duration of breastfeeding and a few weeks thereafter. So there are lots of options. I'm trying to really individualize, um, but There are lots of options. And the reason that there are lots of options right now is that we don't have a lot of data from the United States because we've been telling people not to do this. That doesn't actually mean that they haven't been doing this. I think a lot of people have been breastfeeding and not talking to their doctors about it, but it means that in the US we haven't been collecting data on this. However, there is a lot of data on this from Africa. And we've been trying to make inferences from that. One kind of carryover from the data that we do have is that there is concern for increased transmission risk from mixed feeding, which means that if somebody is both breastfeeding and formula feeding, there is a theoretical increased risk of transmission, and this has come up a lot in my conversations with primary care pediatricians because we do try to recommend. Uh, just exclusive breastfeeding if people are going down that road, but that's hard. And we acknowledge and the guidelines acknowledge that there could be a need for some formula supplementation. And the data that argues against mixed feeding actually is more like really early introduction of solids, like at around age 2 or 3 months. Not so much mixing some formula with breast milk. So we're doing the best that we can with the data that we have. Um, I'm not going to get too into the weeds with some of these studies. Other than that to say, the biggest studies that we have looked at either giving the parent antiretrovirals during pregnancy and breastfeeding or giving the baby antiretrovirals. During breastfeeding, not both things. So that's not something that we're ever gonna do, right? We're never gonna say, OK, mom, like you can stop taking your antiretrovirals and we'll just give babies some medicine. So the data that we have is not perfectly applying to the scenarios that I have. Um, if you end up interested in this reading about this, you might hear about the PROMISE study, um, which is a very important study, and this is, uh, why we do recommend, uh, Uh, extended prophylaxis with navirapine for some babies, especially if we think that there's a chance that, uh, mothers may become viremic later on in the breastfeeding period. I think I'm gonna skip over this, but, uh, again, not getting too into the weeds, but I am not totally convinced that we need to do extended infant prophylaxis if mothers are consistently virologically suppressed and they're on meds themselves. So we've been doing a lot of work, a lot of multidisciplinary work around supporting breastfeeding at children's, uh, starting infant feeding conversations early. Um, we've been talking to Opi about this. There are some Opis who are really, really excited about this work, talking to Adult ID, um, Of course, there are lots of people who are followed by outside providers, uh, so just trying to get the word out about some of these changes. We're navigating, managing these infants given the ambiguity over the best prophylaxis regimens, um, and other risk mitigation strategies, we are working with our OB and our adult ID colleagues to make sure that mothers remain virologically suppressed doing ongoing monitoring while they're breastfeeding, uh, and then again, just trying to spread word about this to stakeholders. Uh, lots of meetings. We now have a monthly meeting. Um, there's just, there's so much going on behind the scenes. If you're ever taking care of a baby who's been perinatally exposed to HIV, um, we do a lot of work during pregnancy to support these families, and then we have a monthly meeting with the adult, uh, HIV docs, uh, with MFM, um. And then we've had discussions outside of that with the hospitalists here and with the NICU, um, on approaching breastfeeding and of course other ways to support these families and prevent perinatal HIV transmission. We do have a guidance document that I recently revised, um. But what we're just trying to promote is starting these conversations early and just having really thoughtful counseling conversations with families. And again, I'm not recommending breastfeeding to everyone. That's not the message, um, but I do really want to support breastfeeding, uh, especially when people are neurologically suppressed. So things that might come up in your conversations with families if you are taking care of any HIV exposed infants whose parents are breastfeeding is that we really do recommend right now exclusive breastfeeding up to 6 months of age versus mixed feeding or early introduction of solids, like I talked about based on some not great data. Uh, but this is what we think the safest approach is right now, acknowledging that some formula supplementation may be necessary. Uh, we definitely want lactation support, um, for these families. There is kind of different from some other scenarios, uh, there is. Concern for increased risk of transmission in the setting of mastitis or cracked or bleeding nipples. So I know the typical counseling if somebody has mastitis is to just like keep breastfeeding through that, but with perinatal HIV worried about increased inflammation, increased transmission risk. So we would recommend against that. Um. And then postpartum support is really, really essential. We all know that having a baby is hard and when you're taking care of a baby, it's really hard to take care of yourself, but these parents need to keep taking care of themselves. They need to keep engaging in their own care. Um, talked a little bit about kind of the range of infant management options, 2 to 6 weeks of zoovidine versus extended prophylaxis. Everybody though needs monitoring. Um, we, I should have had a slide about this earlier, but right now we follow these babies in our clinic for 4 months. So, If they are not being breastfed, so a baby who is perinatally exposed to HIV, uh, I'll get serial PCR tests on for the 1st 4 months of life to prove that they have not been HIV infected. If a baby is being breastfed, we're going to keep monitoring for the duration of breastfeeding and then 6 months thereafter. And we're also going to add in maternal monitoring. So it's just, it's a lot more monitoring and a lot more visits, and that's been hard. We've had challenges, for sure. We've had challenges over the last few years. Uh, some of those challenges have been from our recommendation to try to avoid formula supplementation, which has been really hard for people. Um, anytime we're giving a baby more medicine, there's more risk of medication errors, we all know that. So trying to just do really careful counseling with our meds. Um, and then one thing that has happened and one of the reasons that I like to talk to lots of. People about this is we've had some people who have been really, really eager to breastfeed. It's how they want to parent. They're virologically suppressed. The adult HIV doctors are supportive, we're supportive, and they deliver and somebody who hasn't heard about this, admittedly really, really big update sees them and says, oh my gosh, absolutely not. Um, and so some of our families have been dissuaded from doing this. Do you have a question? OK, I didn't mean to pick on the spot. You look like you made up the question. OK. Um, and then we do talk to people about the importance of ongoing clinic follow-up, and again, this has been hard. OK. So that's what I have about feeding. Any questions about that before I talk a little bit about epidemiology, where we are now? Yes. Yeah. They got different perspectives. Yeah. So the reason that we say that the Oh yes, thank you. Um, so one of the residents was asking why we think that there's still some perinatal HIV transmission through infant feeding, even though a parent may be virologically suppressed, if we know why that is. And I think the answer is that breast milk is really complicated. There's a lot of stuff in it, and there is a H. that can be integrated in the cells that are in breast milk. And even if there isn't a detectable level of HIV in maternal blood, when we look there, there's integrated DNA, uh, integrated HIV into the cells that can be in breast milk. So it just comes down again to breast milk being a really complicated, wonderful thing, um. You guys may have heard about U equals you, this idea that undetectable equals untransmissible. So if your HIV viral load is undetectable, um, and you have sex with somebody, you cannot transmit HIV to somebody via sex. Such an important message. It's such a powerful message, um, for people living with HIV, and we do not think that you equals you is true of breast milk. But I think that there's more data to come. For sure. So we're still learning and in 5, 10 years, I might be here telling you guys something different. Kind of piggyback question, like, have there been like it, and I didn't see it, maybe it's just you didn't included or I just don't know the, the scene of it. Like, is there, like I know like testing breast milk or like kind of that piece of things is like a you're saying it's just so different and like kind of genius. Like, do you like see like like that will be like coming onto the horizon at all or no? The question was, can we Test breast milk, uh, to see if there's HIV in there, and I think the answer is no because I don't think that one test would be very informative to me. Also, I don't think that there's a lab that could do it for me, um, so it would be some like non-standard like research lab testing, but I also think if you tested one sample and you didn't find HIV there, that really wouldn't, uh, reassure me. A good question. Interesting question. OK. So where are we now? Um, we are really, really good at preventing perinatal HIV transmission. Again, this is something that I love about my job. So in the US the number of perinatal HIV infections annually peaked at around 1600 and 1991. In the battle days since then, About 5000 pregnant people living with HIV give birth in the US every year, but there are under 150 cases every year nationwide, and again, the rate of perinatal transmission with current interventions is less than 1%. Uh, locally, we have a program called Project ARC. Have people heard of Project ARC? Is this something that you're familiar with? Project ARC is such an important program in our community, just celebrated its 30th anniversary. So we provide intensive medical care coordination for a lot of people, um, but That group includes mothers and infants, uh, ensure linkage and retention and HIV care and obstetric medical care, and then care and follow-up for exposed infants. We have a big catchment area and we also see a lot of people from outside of our catchment area because for babies for a while we were the only. In town and we're still the only game in town that will see young people infected with HIV. Now Cardinal Glennon SSM is also following exposed babies, so that's been a really nice shift in the last few years, but we're still again the only group in the area that is taking care of youth living with HIV. Importantly, we're supported by the Ryan White HIV AIDS program under HURSA. Um, have people heard of Ryan White? OK. Brian White was a 13-year-old when he was diagnosed with AIDS after a blood transfusion in 1984, was given 6 months to live, and he really beat those odds, uh, faced a lot of discrimination but had a powerful, powerful advocate in his mother, went to school, gained national attention. And lived five years longer than expected, unfortunately, dying in 1990, uh, because we just didn't have truly effective HIV treatment until the mid-19990s. Um, he has had this program named in his honor, the Red NY HIV AIDS program. Um, which provides so many services to people living with HIV nationwide. Truly an essential program providing medical care, medication, support services to help people stay in care, and more than half of all people diagnosed with HIV, about 500,000 people receive help through the Ryan White HIV AIDS program. So again, it goes beyond babies, although I think babies are a really important part of what we do. Um, there are multiple parts to the Ryan White program. Uh, Part A, Part B, Part C, Part D, and Part F. Um, I'm not sure about Part E. Uh, Part D is the part that's focused on women, infants, children, and youth. So my group is the local recipient of Part D funding for Ryan White. That's how we pay for the care that we do. We really want to keep this funding. We're doing really essential work. I would also argue that we are saving everyone money because providing these intensive services during pregnancy and the first year of life for infants, I am confident is so much cheaper than taking care of somebody living with HIV for their life, um, so we need to keep our funding. We have achieved a really dramatic reduction in mother to child infant, uh, HIV transmission in our area. So again, we have a bi-state service region, Missouri and Illinois. Uh, this graph is from Project ARC. It shows, uh, the number of parents we take care of each year in the usually 30 some parents and then the number of, uh, positive infants. We unfortunately have 2 babies. Born with HIV in our region due to issues of delayed diagnosis and pregnancy, so both of these babies were positive at delivery. There was nothing that we could do prophylaxis-wise to prevent them from acquiring HIV, but we haven't had any cases since then in 2024, so far in 2025. Um, we support parents in achieving virologic suppression, 92%. Of the mothers that we followed in the last 5 years achieve virologic suppression, which is the most important thing in preventing perinatal transmission, and then we provide follow-up for lots and lots of babies, again, at least 3 or 4 months or longer if they're breastfeeding. One just thought that I wanted to bring to this group is that after babies have been demonstrated to not have HIV, so once we do that 4-month PCR and we say, you officially do not have perinatal HIV, you have graduated, congratulations. Uh, we don't continue to follow those babies, but you do. Um, and we don't have a ton of data about these babies. I do wonder if they need closer neurodevelopmental follow-up. Everyone worries that there could be some sequelae from antiretroviral exposure, which is part of why we're moving towards these shorter regimens. Although, of course, I think the benefits of not getting HIV outweigh the risks of getting antiretrovirals for a few weeks. Um, but there is some data out there, uh, that these babies who are HIV exposed but uninfected, some people call these babies HEU. Um, have a higher risk of general morbidity and mortality. There's a possibility of immune system dysfunction. There's a possibility of changes in growth or metabolism, and there are some possible neurodevelopmental differences also. Um, maybe some mitochondrial toxicity could be related to the medications to which they're exposed. Maybe an increased cancer risk, although I don't think that there's any strong data for that. Um, so just something to think about if you're seeing these babies in your clinic. Um, and a group that I'm just trying to think about, is there more that we could do. Um, And there is some guidance in the national HIV guidelines available at clinicalinfo. HIV.gov, just recommending a little bit of thought for these babies if they experience some uh sort of unexpected symptoms after they conclude their HIV care. Here are some resources. So I went through these slides pretty quickly, but you can always page pediatric ID on call. Always reach out to me personally. The perinatal HIV guidelines are readily available also, clinical info. HIV.gov, incredible resource. There's also a really wonderful resource in the National Perinatal HIV AIDS hotline, which has run out of. CSF, uh, they take calls from any providers nationwide who have questions about how best to care for an HIV exposed infant. Um, so they are the people that I reach out to if I'm not sure what to do. Um, they have, uh, just a lot of resources, a ton of expertise. Uh, they're also a group that needs to keep their funding, um, so just something to think about, um. And then the IASUSA might be a little in the weeds, but that's a uh professional continuing education organization focused on HIV and some other viral infections. They have fabulous resources including, uh, a lot of resources on breastfeeding. And I have lots of other sources that people are interested.
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