We learn about the history of reduction of mother-to-child transmission of HIV, and current recommendations for evaluation and management of the newborn. We are joined by Amanda Evans, MD, Assistant Professor of Pediatric Infectious Disease at the University of Texas Southwestern Medical Center.
Dr. Neeta Goli:
Welcome to Newborn News, a podcast where we discuss educational topics for medical professionals who care for newborns. I'm your host, Dr. Neeta Goli, a pediatrician in the UT Southwestern Newborn Nursery. Welcome back to the podcast. In today's episode, we'll review the management of newborns with perinatal HIV exposure. We're joined today by Dr. Amanda Evans, the Medical Director of the ARMS Clinic at Children's Health in Dallas and Assistant Professor in Pediatric Infectious Disease at UT Southwestern, which provides care for infants, children, and adolescents who are exposed to, or living with HIV. Dr. Evans, thanks for joining us today.
Dr. Amanda Evans:
Thank you so much for having me.
Dr. Neeta Goli:
So to start off, can you tell me a little bit about the ARMS clinic? What does that stand for?
Dr. Amanda Evans:
So the ARMS acronym stands for AIDS-Related Medical Services. The clinic was established 31 years ago, and it has been serving infants and children and adolescents in the North Texas area. A lot of the staff have been dedicated and have been with us, with our clinic, for many years. We have a nurse practitioner actually, who has been with our clinic since its inception. So it was started by Janet Squires, who was a physician who actually started the child abuse clinic and the ARMS clinic back in the eighties when the HIV epidemic first hit Dallas.
Dr. Neeta Goli:
So that's a wonderful resource. We're really lucky to have you guys available to us.
Dr. Amanda Evans:
Thank you.
Dr. Neeta Goli:
Well, thanks for coming here to talk to us about this today. Can you tell us a little bit about the history of the incidence of perinatal HIV exposure and transmission?
Dr. Amanda Evans:
Yeah. So when you're thinking about the reduction of maternal to child transmission of HIV, it's important to think about where we start without any antiretrovirals. And there've been many studies that have looked at just the natural history and a lot of studies that have compared antiretrovirals to placebo. So if you're thinking about the rate of maternal to child transmission of HIV, so what would you guess the rate would be?
Dr. Neeta Goli:
Off the top of my head, I don't have a good percent answer.
Dr. Amanda Evans:
It's approximately one in four, so 25%. And various studies have varied between 15 to 42%, but on average, about 25%. So there have been a lot of studies since we first noted back in the early eighties that children can acquire HIV from their mothers, but in 1994, there was a groundbreaking clinical trial and it was called the PACTG 076 study, the Pediatric AIDS Clinical Trial Group, it's a clinical trial. And it looked at three arms of pregnancy, labor, and then also postnatal management of the infant, to try to reduce the maternal to child transmission of HIV. So when you're thinking about things that we do and this clinical trial looked at... so we have baby, mom, and back in the eighties, and in the nineties, they started out with one drug that was FDA approved. They didn't quite know at that time if this drug was safe during pregnancy, so there are many clinical trials looking at short term or long-term therapy. So this particular one started at 14 weeks and continued medication throughout pregnancy. It was considered one of the longer durations.
Dr. Amanda Evans:
This was given, AZT was given by mouth to moms during pregnancy, and then they continued it, AZT, during labor and delivery. Typically, moms are NPO during labor and delivery, so it was given IV. And then they switched over to baby after baby was born and gave it by mouth to baby for six weeks. So after they did that, they saw, they analyzed some of the studies and they saw about 67% reduction in the rate of infants that were born with HIV infection as compared to the placebo. So there was a really good response in the reduction in using these three branches of medication. So this went down to 8%.
Dr. Amanda Evans:
So, of course, 8%, isn't the national rate of transmission of HIV right now. So we have a transmission of approximately 1% nationally. And so there's a number of things that we do today that have built upon this basic concept, but we have advanced our therapy since then. And number one thing is that we like to identify parents and mothers in particular, that are HIV positive. So we screen them during preconception ideally, and get them started. So preconception counseling, if a woman desires pregnancy, then get her HIV tested, get her started on medication. So we no longer use monotherapy anymore, we start on HAART or on triple antiretroviral therapy. The whole goal to that is to bring her HIV viral load down to undetectable status. And so if we can bring that down to zero, close to zero, then we can really reduce the baby's vertical transmission rate.
Dr. Amanda Evans:
We still continue antiretrovirals throughout labor and delivery for mothers that have viremia. We still give AZT via IV during labor and delivery. And then we continue antiretrovirals to baby post-delivery. Although there've been many advances in using shorter therapy for babies that are at low risk. So we've gone from six weeks of therapy, we've now cut this down to four weeks. And this has reduced our number of babies that have low neutropenia, so low ANCs. And it's reduced the number of babies that are experiencing anemia, both complications from zidovudine. However, babies that are at higher risk of transmission, so in particular moms that show up at labor & delivery with a new diagnosis of HIV, or if they are diagnosed late in pregnancy, this is going to be a category of high risk.
Dr. Neeta Goli:
And then what about maternal viral load at the time of delivery?
Dr. Amanda Evans:
So we've identified most recently that this third trimester is a really critical point and their risk for maternal transmission to infants really increases as you go through pregnancy. So it is lower in the first trimester, but then really your rates increase as you get to the third trimester. So if you are viremic, if mom has a positive viral load in that third trimester, then these are the infants that you need to think about having combination prophylaxis during their postnatal period. So we use a combination of either two to three drugs for baby.
Dr. Neeta Goli:
So functionally for us taking care of newborns, if we have a baby who is high-risk, we should always be consulting with you all, with our specialists to get input on whether or not they need the combination therapy, which exact drugs and for what duration?
Dr. Amanda Evans:
Mm-hmm. The US DHHS current guidelines for mothers specifies that after 36 weeks, if a mother has a viral load that's greater than 50 copies, then you should contemplate, you should identify those infants as using combination therapy. We don't clinically have good placebo-controlled randomized clinical trials that identify, which is better: two drugs versus the empiric HIV prophylaxis, which would put a baby on three drugs. So that still is left up to the clinician to use your best clinical judgment on their risks.
Dr. Neeta Goli:
What other special precautions or interventions should we take for these babies when they're in the nursery?
Dr. Amanda Evans:
So we know that moms that are HIV-positive can be at risk for opportunistic infections and reactivation of opportunistic infections. So it's important that during their history or during your history taking of these babies, to look back at their maternal record, to go through carefully and see if moms have been positive for other opportunistic infections, HSV, toxoplasmosis, hepatitis B or C, and including CMV. If they are having any of these opportunistic infections, we can first clinically screen them. And then also as warranted, if there's any signs on their physical exam order the appropriate screening test for them. For moms that are serologically positive for toxoplasmosis during pregnancy, we typically follow serology on those infants and for infants, we also check to see if they have CMV in their urine, if they're shedding CMV.
Dr. Neeta Goli:
So for these babies, in terms of lab work that we should routinely be checking for these babies. So HIV DNA versus RNA PCR, CBC, a urine CMV PCR, if possible, and the toxo serology, like you mentioned, if indicated. Can you tell me a little bit more about the CBC specifically? What are we looking for?
Dr. Amanda Evans:
So I would order a CBC with a differential, specifically what we're looking for in later stage and when we're following up these babies is that their risk for neutropenia and anemia, and occasionally they'll develop an issue with their platelets. So at that baseline, that CBC with a differential helps us to determine where they're starting from. And so when we follow them up in the clinic at a month or two to four weeks, and repeat that CBC, we're able to see if they've significantly dropped from there. And it depends on your availability in your hospital, if you have access to HIV DNA PCR, or if you need to do an HIV RNA PCR. In general, they're equivalent, there are certain circumstances particularly if a baby's on combination prophylaxis or in which there have been some historical studies suggesting that the HIV DNA PCR may have less false negatives.
Dr. Neeta Goli:
So we talked about the lab work. We talked about when to consult you all in the ARMS clinic, our specialists, what about feeding for these babies?
Dr. Amanda Evans:
So in general, in the US, breastfeeding is not recommended. Formula feeding does reduce the risk for transmission of HIV, to these babies. And we have good federal programs that can provide formula for low-income or resource-poor families. Also, another option for families that wish to look at is milk bank, if families are interested in getting breast milk for their infant, so there are donor milk options. But even a mother with an undetectable status, breastfeeding still carries, we cannot eliminate risk of transmission of HIV in a mom that has an undetectable status. So we have had a couple of moms that have delivered at Parkland recently that we have been following. And in that circumstance, I think we have to be very vigilant in our counseling, both during pregnancy and while they're in nursery to reiterate our recommendations. And then if a mom still chooses to breastfeed, then she has to undergo a lot of testing postnatally to make sure that she's maintaining a low viral load. And then also the baby requires additional screening.
Dr. Neeta Goli:
And then I know at Parkland, we typically routinely bathe this infants before all their injections, all the eyes and thighs and everything are given, but you just let me know about some actual evidence behind it.
Dr. Amanda Evans:
So in looking at the details of the DHHS perinatal guidelines, there is a statement that says that currently there is no clinical evidence that would give guidance on bathing measures or when would be appropriate to do a circumcision in these babies.
Dr. Neeta Goli:
All right. And then what interventions do we need to undertake before babies can go home?
Dr. Amanda Evans:
It is very important to think about the first four to six weeks in these babies, especially in a mom that may be struggling with just bringing a new infant home into her home and having to ... She might be dealing with a C-section or have other kids. And so these medications that this baby is going to be on postpartum, whether they be two drugs or just monotherapy are not readily available in the community. So you can't take your prescription and it's not like amoxicillin that you can just stand and wait at that Walgreens and get it filled. These typically take 48 to 72 hours for an outside pharmacy to fill. So typically, we would encourage a hospital to dispense from their outpatient pharmacy and to make sure that mom has medication in hand before baby is discharged. That if they don't have that capability from their outpatient pharmacy, then at day of life zero or one, once baby's born, and you have an idea of what therapy that baby's going to be going home on, on day of life two, we would make the recommendation to go ahead and send that script out to that outpatient pharmacy so that they have a lead time to get that filled.
Dr. Neeta Goli:
And then once these babies are discharged home, since we're so lucky to have the ARMS Clinic here nearby, what services do you provide for these families?
Dr. Amanda Evans:
So the ARMS Clinic has had a tradition of providing both primary care and specialty care, and particularly for HIV-exposed infants. There is, and there has been and there continues to be a concern for both the initial and the late effects of antiretrovirals. And in addition, these families often have multiple siblings, so we provide HIV testing during the first 18 months, we provide all of their primary vaccination series. And then as an infant, if they choose to go to an outside pediatrician, we can of course graduate them to the community pediatricians. But if mom has another infant on the way or another sibling, we try to keep the family unit together and provide that continuity of care through our clinic.
Dr. Neeta Goli:
So you functionally act as the medical home while these children are young.
Dr. Amanda Evans:
Yes. And now that we've been open and this epidemic has been going on for three decades and we have effective therapy. We are lucky enough to, in a sense, have second-generation parents. So our perinatally infected children are now mothers, and we are now seeing their children. And by large, their children are growing up healthy and uninfected. But these are very complex perinatally-infected moms that may be on multi-drug regiments, but it of great pleasure to take care of their children.
Dr. Neeta Goli:
Absolutely. To end the episode, do you have any tips for our listeners while taking care of newborns?
Dr. Amanda Evans:
The only other thing I think that comes to mind is that these mothers, they deal with a lot of stigma around their diagnosis and may not be readily open to discussing their diagnosis, especially around even close family members. So I would just make everybody aware of that, that even their partners or their siblings, may not be aware of their diagnosis. So all this to be just little cautious when speaking with their families, but they are a great pleasure to take care of.
Dr. Neeta Goli
Thanks so much. This has been really educational. Thanks for joining us today.
Dr. Amanda Evans:
You're welcome.
Dr. Neeta Goli:
Thanks for listening to Newborn News. We hope you join us next time. If you like what you hear, make sure to subscribe and leave us a review. If you have questions, comments, feedback, or suggestions for future episodes, please email me at NewbornNews@utsouthwestern.edu. As a reminder, this content is educational and is not meant to be used as medical advice, views or opinions expressed in this podcast are those of myself and my guests, and do not necessarily reflect the views of the university.