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In early March, the HIV community was stunned by a headline it had waited more than two decades to see: a baby in Mississippi had been “functionally cured” of the HIV virus. The medical team behind the research was led by Dr. Deborah Persaud, a virologist at Johns Hopkins Children’s Center in Baltimore. Kojo talks with Persaud about what her research means for HIV treatment locally and globally, as well as how her career brought her from Guyana to the peak of pediatric medicine.
- Dr. Deborah Persaud Associate Professor of Pediatrics and Infectious Disease, Johns Hopkins Children’s Center
MR. KOJO NNAMDIFrom WAMU 88.5 at American University in Washington, welcome to "The Kojo Nnamdi Show," connecting your neighborhood with the world. Later in the broadcast, take time to enjoy Time For Three, an in-studio performance by a classical jam band. Yep, you heard me right, a classical jam band in studio. But first, in early March, news that the world had been waiting more than two decades to hear swept the headlines.
MR. KOJO NNAMDIAn HIV-positive baby in Mississippi had been functionally cured of the virus. This medical milestone which started with treatment less than two days after the baby was born involved a trio of researchers, led by Dr. Deborah Persaud of Johns Hopkins University. Dr. Persaud has spent her career zeroing in on how the virus hides out, how it mutates and how it resists treatment. And now, Time magazine has named her one of the most 100 -- one of the 100 most influential people in the world.
MR. KOJO NNAMDIShe also happens to be a native of my home country, Guyana. Dr. Persaud joins us in studio to talk about her work and what brought her from Guyana to the pinnacle of medical research. Dr. Persaud, thank you so much for joining us.
DR. DEBORAH PERSAUDThank you for having me here.
NNAMDIDeborah Persaud is a professor of pediatrics and infectious disease at Johns Hopkins Children's Center in Baltimore. If you'd like to join the conversation, give us a call at 800-433-8850. You can send email to firstname.lastname@example.org. Send us a tweet, @kojoshow. Have advances in HIV therapy made us complacent about the disease? Call us, 800-433-8850. Deborah Persaud, one of Time magazine's 100 most influential people in the world, what does that feel like?
PERSAUDIt's actually incredible to be on the same list as our president and first lady. I never imagined we would end up in this position.
NNAMDIWell, a lot of people believe you deserve it because of what you have done, so let's talk about what you have done. The study you published about this baby born in Mississippi garnered international headlines, and I think a lot of people thought it meant you'd found a cure for HIV. What does it mean to functionally cure a baby?
PERSAUDI appreciate you asking that question. So we use the term functional cure, first of all, because the infant has only been off therapy for 12 months now. And to be functionally cured of HIV would mean that a person who was known to be HIV infected received an intervention, such as an antiretroviral drug cocktail in this case.
PERSAUDAnd then the treatment was able to be discontinued where the infant or toddler did not develop rebound of the virus in the bloodstream. And so for all intents and purposes, the child has achieved a state of what we would call HIV remission, so it has -- we've been able to control the virus to the point that we can not detect the virus replicating in the baby's blood system.
NNAMDIIn this country, pregnant women don't generally pass HIV along to babies because they're treated before they give birth, but this Mississippi baby was born with HIV. So how was the treatment of this infant different from how babies born to HIV-positive mothers are usually treated after birth?
PERSAUDYeah. That's a great question. And so you're right. In this country, pregnant women are identified, and this is a key point. It's -- and a key point that I want to emphasize is that pregnant women really should continue to be tested so they can be identified. And if they're identified as infected, that they can get the appropriate treatment to prevent transfer of the virus to the infant.
PERSAUDSo you're right. In this country, routinely, we give babies antiretroviral drugs to prevent the virus from establishing itself or setting a foothold in the baby's system. And so the drugs that we use depend on what we can -- how high risk we consider the infant to be. So in other words, in a mother who's been engaged in care, received care during the pregnancy, most women would get the drug cocktail for treatment of their infection.
PERSAUDAnd such babies only get a single drug for six weeks, and that drug is called AZT or zidovudine, and it's given every day to the baby for six weeks. Now, when infants are high risk for infection, so as in the case of the Mississippi child where the infection was not known in the mother, the infection was actually diagnosed during the delivery process. And that's standard for this country.
PERSAUDIf a woman presents in labor and has not had an HIV test, a rapid HIV test is done, really to identify whether she's infected to be able to give the infant drugs after the baby is born and if possible to give drugs during the labor and delivery process. So the Mississippi child would be considered high risk for infection because the mother's infection was not known. And so she did not receive antiretroviral drugs.
PERSAUDAnd so in that setting, we use more than one drug. Now, what our guidelines recommend is to use two drugs, AZT, that we standardly use, and then the second drug that's used is nevirapine. And that's usually given in a three-dose schedule over the first week of life. Now, some experts would use three drugs for high-risk infants, AZT, 3TC and nevirapine. And so the Mississippi child, the pediatrician caring for her, Dr. Hannah Gay at the University of Mississippi, considered this infant high risk.
PERSAUDShe is the HIV specialist in Mississippi, and so she started a three-drug regimen. But what's different about this regimen is that she gave the drug regimen twice a day in the form of a treatment regimen rather than in a form to prevent infection or for prophylaxis of the infant. Now, in doing that, she quickly did several tests to really be able to identify very early whether the baby was infected or not.
PERSAUDObviously, you don't want to continue multiple drugs in a baby who's not infected. And so really within the first week of life, she already had definitive evidence that this baby had replicating HIV in the blood system, meaning that we could detect RNA using our standard (word?) or test that we use to monitor infection in infected babies and infected individuals.
PERSAUDAnd so with that, the prophylaxis regimen was not stopped. The treatment regimen was really continued throughout the first 18 months of life when the child was lost to follow-up and then brought back into care when she realized or she was told by the care providers that the baby was no longer receiving the antiretroviral drug cocktail.
NNAMDIAnd so she brings the baby back and what?
PERSAUDSo it's standard. If you get a report from a parent that a child's gone off therapy -- I mean some kids it's not the parents stopping the drugs. Some kids refuse to take the medications. As they get older, you can't force them to take medications. And so what we do standardly in clinical care is you check where you are with respect to the infection. So you run the battery of tests. You check what the viral load is, what the CD4 count is.
PERSAUDAnd so that's exactly what she did. She got a viral load on the infant, and it came back as undetectable. Now, what is undetectable means -- it means our assays can detect virus up -- and the assay that she used detect virus in the blood over 20 copies per mL. So she received a test result that came back as undetectable. Obviously, as care providers, when we get results that don't fully make sense, we repeat the tests to be sure that there was no sample mix-up or lab error, so she repeated the test a few weeks later.
PERSAUDAnd again, it came back undetectable. So, of course, she thought is this baby -- was this baby really infected or not to begin with? So she looked for antibodies to the virus, which we know infected developed antibodies to HIV, and that's the standard test that's used in older children to detect infection, children over 18 months of age, and the antibody test came back negative. So she did additional tests because she couldn't believe that there's no virus present with respect to the viral load.
PERSAUDThe antibody test is negative. So she did what's called an HIV DNA PCR, and that's the test that we used to really identify infection in an infant. That's a test that shows that the virus' nucleic acid is embedded in the cells of the infected person. And so when she repeated that test, it came back negative. Now, at this point, and the toddler has been off therapy for five months, we have extensive experience in the field that when kids go off drugs, the virus just rebounds.
PERSAUDSo we would caution parents not to stop antiretroviral drugs in their children. This is a unique case. It's a single case. As you started the show, it's really galvanized the field and the world with respect to and has given a lot of hope, but it come with a lot of hype. And I think we need to be able to replicate this to fully understand are we dealing with something that we can apply to infants around the world and even within the United States, or is this just a red herring or something very unusual. And we're really trying to replicate these findings in an expeditious manner.
NNAMDIOf course, there is such a temptation to hype because people want to know could these results bring about new treatment protocols for children in the -- on the continent of Africa where there are so many more HIV-positive babies?
PERSAUDYes. And I think not only in the continent of Africa. I think it's important to remember -- when you're in the D.C. area, it's important to remember that...
NNAMDIWe have high levels here many countries in Africa.
PERSAUD...you have some of the highest levels here in the D.C. area. But I think we do need to remember that we don't have zero infections within the United States. In fact, they're somewhere between 130 to 150 infants still infected within the United States. So, yes, we're actively trying to develop a clinical trial, and this is being done in -- through the International Maternal Pediatric Adolescent Aids Clinical Trials Network or the IMPAACT Network.
PERSAUDThat's funded by the National Institutes of Health to really look at high-risk infants born in the United States and in international settings where the burden of infection is to really examine this very concept, and that is if you treat an infant very early before the virus has had the opportunity to really set and lay down these reservoirs or hideouts whether we can achieve cure, meaning that we can stop antiretroviral drugs at some point, and we haven't quite decided what that time point will be.
PERSAUDIn the Mississippi child, it was about 18 months of age, and so we're still in the process of trying to identify how to develop these clinical trials to assess cure.
NNAMDIOur guest is Dr. Deborah Persaud. She's an associate professor of pediatrics and infectious disease at Johns Hopkins Children's Center in Baltimore. She was the leader of a tri of researchers conducting research that eventually led to an HIV-positive baby in Mississippi being functionally cured of the virus. We're going to take a short break. If you like to join the conversation, give us a call at 800-433-8850. Do you think we'll see a cure for HIV-AIDS in the next decade or two? You can also shoot email to email@example.com. I'm Kojo Nnamdi.
NNAMDIWelcome back. Our guest is Dr. Deborah Persaud. She's an associate professor of pediatrics and infectious disease at Johns Hopkins Children's Center in Baltimore. And, of course, the question that springs to minds of most people when they hear the results of what happened in Mississippi is, what do your findings with the Mississippi baby for adults who are HIV positive?
PERSAUDYes. So we've been asked this question a lot. And obviously there's a big difference between infections in infants and adults and that is we know when babies are infected to the virus. We know mothers are pregnant, and that's when they're exposed. They're exposed during the pregnancy process, during labor and delivery and if they breastfeed through breastfeeding.
PERSAUDSo in this country, we -- because it's safe to feed infant's formula, we recommend HIV-infected women not to breastfeed their infants. So what's -- in terms of its applications for adults, it's hard to know when -- this early when an HIV-infected -- when infection occurs in an adult. And so we think that it would probably take a while before our findings have widespread applications to adults and, again, if we can replicate the case.
PERSAUDBut I will say there is emerging -- there are emerging data that treating infection early in adults really has an effect on these viral reservoirs and to the point where there are unique cohorts of patient or adult patients being described who are treated very early infection. So what's very early? Within a few weeks of infection in which these viral reservoirs appear to have been curtailed or are smaller, allowing a small subset of patients.
PERSAUDSo 5 percent of patients in a very famous cohort now known as the Visconti cohort have been treated very early, and these are adult patients and have gone off antiretroviral therapy and has been off therapy for about five years now. So in essence, we now -- there has now been identification and reports of this unique cohort of patients, adults treated early who've been able to go off therapy, so in essence, are considered functionally cured.
PERSAUDSo we think together these small pockets of cases represents potentially that we may be able, if we can identify infection early enough in adults, perhaps a similar outcome can be achieved.
NNAMDIPut on your headphones, please, because now we're going to go to Kate in Washington, D.C., who has a question for you. Kate, you're on the air. Go ahead, please.
KATEYeah. Hi. I was hoping you could clarify how the baby in the Mississippi case did not have any antibodies to the (word?) that she had previously shown positive for.
PERSAUDYeah. That's a really good question. And we know from our studies. We've done therapy trials. In fact, one of the scientists or collaborators on the study of the Mississippi child, Dr. Katherine Luzuriaga, who's an immunologist at University of Massachusetts, described this phenomenon in children, and that is we -- what standard of care is that infants are treated as soon as infection is identified.
PERSAUDSo if you live in a country such as the U.S. where we can identify infants as early as six weeks of age or even four weeks of age and you start therapy early, and you're able to block the virus from replicating within the bloodstream of that infant, then, in fact, those infants never developed an antibody response to HIV. So you need to have exposure and extensive replication of the virus to develop an antibody response.
PERSAUDAnd by treating very early, you blunt that response, and it just does not happen. So, in fact, I'm glad you asked that question because there are kids around this country who've received antiretroviral therapy now from two months of age and have been on therapy for 14, 15. We've identified some 18 years of age.
PERSAUDAnd, in fact, we presented this work at CROI, and they're still HIV antibody negative. And so it doesn't mean they're not infected. It means that their virus has been so controlled that they're unable to generate or have an antibody response. So you can't use the antibody test to identify infection.
NNAMDIKate, thank you very much for your call. These results must have been particularly gratifying for you since you were in New York City at the beginning of the AIDS crisis, treating patients in the early 1980s. Can you tell us a little bit about your background and what inspired you to go into this field?
PERSAUDSo I think anyone working in the field of HIV/AIDS who have lived through the emergence of this epidemic in the '80s has to be affected by it. And what was striking about this as a medical student at NYU Medical Center, I encountered -- actually, I remember vividly my first case was a 20-year-old who presented with appendicitis and turned out to have Kaposi sarcoma, and that was the presentation.
PERSAUDKaposi sarcoma is cancer of the intestine in this case, and that was his presentation. Now, shortly after that, we started having infants. And, you know, these infants, you can recognize them across the room. They're about two to three months of age and were having difficulty breathing and had this classic profile of being wasted and thrush. And so that was -- or how HIV presented in infants at the time, and all of those kids died.
PERSAUDIn fact, very few survived because we didn't have antiretroviral drugs. And so I've lived through this epidemic to a point where we didn't -- we used, actually, CD4 ratios. We didn't have antibody tests at the time and just watched the progress that has been made, not only within resource-rich settings but resource-poor settings based on our PEPFAR programs, and it's really remarkable. And I think the best description for my career path is really being in the right place at the right time.
NNAMDIYeah, because you're now involved in admitting aspiring doctors at Johns Hopkins. How does your early experience as an immigrant student affect how you select incoming students?
PERSAUDWell, I -- actually, I'm humbled when I select incoming students because the bar is so high. I often wonder how did I make it into medical school in the United States having just moved to this country when I entered college and attending a city university that not many people know about your college within Jamaica Queens, N.Y. But you realize that what it takes is really perseverance and convincing those at the other end that you do have a mission and a goal in your life.
PERSAUDAnd I'd like to encourage young people out there to really stay focused. But I think that the bar is so high in the educational system. I mean, I watch my kids, they're so with the Internet and access to information. They're so knowledgeable that it's easy to select. In fact, it's hard to reject applicants at this point. It's easy to find very talented individuals committed to this charge.
NNAMDIAnd so you give a lot of credit to being in the right place at the right time?
PERSAUDBeing in the right place at the right time and having the right mentors. I think throughout my life, I've been fortunate to have teachers and mentors all along the way, even to this point at -- in the Johns Hopkins community, to continue to support and mentor my work and even outside with the collaborations I've established through the -- my involvement with the impact network.
NNAMDIThere's a lot of concern about complacency and HIV, especially among young people who do not remember that a diagnosis used to be a death sentence until there's a complete cure for the virus. What do you hope HIV positive people will take from your research?
PERSAUDWell, I think the main message is this is a single case of cure, but it certainly informs us with respect to future directions towards cure. I mean, this is -- our global mission is elimination of HIV/AIDS, and I think it's just one approach towards achieving this goal. But the main point is, first, prevent yourself from getting infected, and that should be our main message. We know how to prevent adults and children from getting infected, and we need to use those strategies.
PERSAUDAnd the second is if you're unfortunate to get infected, we know that therapy, really, can prolong the survival. And, in fact, HIV infected patients are dying from what you and I will die from, heart disease and cancer and kidney disease. And so it's important that they take the cocktail of antiretroviral drugs because these are effective in suppressing the virus and prolonging life and, importantly, in preventing transmission to other individuals to really contribute as a whole to preventing spread of the virus.
NNAMDIWell, now that TIME Magazine has named you one of the most -- the 100 most influential people in the world, you know that you are honored by your adopted country. And if my Facebook page is any representative, your native country is also extremely proud of you. And so that means -- and especially since this is a contribution to world medicine, then the whole world is proud of you. Deborah Persaud is an associate professor of pediatrics and infectious disease at Johns Hopkins Children's Center in Baltimore. Congratulations. Thank you so much for joining us. Please keep on doing your work.
PERSAUDThank you very much Kojo. It was a pleasure to be here.
NNAMDIWe're going to take a short break. When we come back, a classical jam band, that's right. Time for Three joins us in studio with a live performance. I'm Kojo Nnamdi.
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