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Transcript: NICHD Research Perspectives—July 19, 2012

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Announcer: From the Eunice Kennedy Shriver National Institute of Child Health and Human Development, part of the National Institutes of Health, welcome to another installment of NICHD Research Perspectives. Your host is the Director of the NICHD, Dr. Alan Guttmacher.

Dr. Guttmacher: Hello, I'm Alan Guttmacher. Thanks for joining us for another in our monthly series of podcasts from the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health.

The 19th International AIDS Conference will begin in Washington, D.C., this Sunday, July the 22nd. Through this podcast, we would like to underscore the importance of this conference by acknowledging some relevant recent research supported by NICHD's Pediatric, Adolescent, and Maternal AIDS Branch. The branch supports and conducts both domestic and international research into HIV infection and its complications in infants, children, adolescents, women, and the family unit as a whole. My guests are Dr. Lynne Mofenson, who is the chief of the branch, and Dr. Bill Kapogiannis. We'll talk with them today about several recent studies from the branch: first, findings to reduce the occurrence of mother-to-child transmission of HIV; next, the safety of one of the new anti HIV drugs, tenofovir, during pregnancy; and, finally, the risk of bone loss among young men newly diagnosed with HIV.

Before we get to the research, however, I'd like to begin by congratulating Dr. Mofenson on her nomination for the Samuel J. Heyman Service to America Award. Lynne was nominated for this prestigious award for her pivotal role in preventing the AIDS epidemic among children—through her leadership in developing clinical trials to prevent mother-to-child transmission of the AIDS virus. Lynne also helped launch a study of the anti-HIV drug zidovudine, or AZT, as a means to reduce the chances that a pregnant woman with HIV would pass the virus on to her baby. That study reduced mother-to-child HIV transmission from 25 percent to 8 percent. Since then, she has been instrumental in numerous other studies to reduce mother-to-child HIV transmission, playing a large role in reducing the transmission rate to where it is today, at less than 1 percent in the United States. That number really bears repeating—less than 1 percent—because not so long ago, we would have thought it unimaginably low. Lynne has also worked with representatives of numerous federal agencies to shape federal policy and develop treatment recommendations for women and children with HIV.  Lynne, could you tell us something about the situation regarding mother-to-child HIV transmission and what it was like in the 1980s when you began your studies? How does that compare to the situation today? And what are some of the advances that led to the change?

Dr. Lynne Mofenson: Sure, Alan, and thank you very much for the kind words. When I came to NICHD in 1989 there were over 2,000 new pediatric infections a year in the United States—25 percent: that's one in every four infected mothers passed infection to their infants and 25 to 30 percent of these infected children died before age 1 year. And I remember walking with my family in D.C. near the White House around that time when the AIDS quilt was being displayed and seeing a quilt from a young child that I'd seen at the clinical center just a few weeks earlier. So HIV was a horrible disease: it was killing both mothers and babies. And in the early 1990s, in collaboration with NIAID, we developed the first clinical trial to prevent mother-to-child transmission using the only drug available at that time, zidovudine, given to both pregnant women and their infants, and giving this drug to pregnant women was highly controversial. Yet we had a fatal illness that was being transmitted from mother to child. And in February 1994, President's Day weekend—I'll never forget it—the Data and Safety Monitoring Board stopped the trial early as AZT had reduced transmission by an amazing 70 percent. Following this, I led a DHHS group to move these research findings into clinical practice. We published initial guidelines in only 2 months, followed by formal guidelines only 4 months later, in August. We worked with multiple DHHS agencies in rapidly implementing these guidelines, including the FDA to obtain drug approval, Medicaid to provide drug availability, and the CDC to promote universal testing in pregnancy. And within a year, we saw transmission in the U.S. decrease from 20 percent to about 5 to 8 percent. And then further research conducted by our group showed that use of two or three anti-HIV drugs was even more effective than using AZT alone. And with current regimens, treatment is now less than 1 percent in the U.S. and less than 100 children a year are infected.

Dr. Guttmacher: Thank you, Lynne, for reminding us really how terrible and seemingly implacable the epidemic was in those days—they weren't that long ago—and the role the research has played in really changing the picture so dramatically. I know you are an author, along with Dr. Heather Watts of NICHD and other colleagues, of a recent study to further reduce the incidence of mother-to-child HIV transmission. That study was published in the June issue of the New England Journal of Medicine and sought to reduce mother-to-child HIV transmission among pregnant women who don't even know they have HIV until the virus is detected during childbirth. These women have obviously missed the chance for the early treatment needed to keep the virus from being passed on to the baby. Can you tell us something more about that study?

Dr. Mofenson: Sure. So the study enrolled HIV-infected women who were diagnosed either during labor or immediately after birth, so they didn't receive any anti-HIV drugs during pregnancy and their infants were at very high risk of infection. And the standard regimen was to give the infant 6 weeks of AZT, but we thought that perhaps giving combination regimens might be better. We enrolled over 1,700 mothers and infants, and they were randomized to either one drug (AZT alone), two drugs (AZT with a drug called nevirapine), or three drugs (AZT, 3TC, and a drug called nelfinavir). And at 6 months, the risk of transmission during the birth process was reduced by 50 percent, from 5 percent to 2.2 percent with two drugs and 2.5 percent with three drugs.

Dr. Guttmacher: So what are the reasons why one might use to choose among the combination drug treatments?

Dr. Mofenson: Both two and three drugs seemed equally effective, but the three-drug regimen was associated with more adverse effects in infants. There were more infants with severe anemia and low white cell count with the three-drug regimen and, therefore, the current U.S. guidelines recommend the use of the two-drug regimen when the mother hasn't received any drugs during pregnancy.

Dr. Guttmacher: So your study involved women who were able to formula feed their infants. What is done in poorer countries, where women often breastfeed their infants because formula is not even available?

Dr. Mofenson: HIV can be transmitted through breastfeeding so we need a different approach.  And in a breastfeeding population, as much as 40 percent of the infants can be infected and about 40 percent of this occurs through breast milk transmission. And so our international research has focused on prevention of breast milk transmission. And NIH research has shown that two approaches are effective in reducing transmission through breastfeeding and can reduce the risk from 20 percent to under 2 percent giving an anti-HIV drug nevarapine to the infant every day while breastfeeding or giving the mother a three-drug regimen every day while she's breastfeeding. And as a result of this research, UNICEF and WHO are now recommending these regimens in international settings and are calling for elimination of new pediatric infections by 2015, which is something that I could never have envisioned possibly happening in 1989.

Dr. Bill Kapogiannis: So Lynne, there has been concern that strains of the virus are growing resistant to some of the drugs used to prevent transmission. Was this antiretroviral resistance a factor in your study?

Dr. Mofenson: That is a very good question. Bill. We looked at the presence of drug resistance in the infants who became infected despite getting infant drugs, and we didn't see any difference in resistance between the one-, two-, or three-drug regimens.

Dr. Guttmacher: Lynne, the study you just told us about shows us how to prevent transmission when women do not know that they have HIV until they are in labor. However, we certainly know the best way to prevent mother-to-child transmission is to begin anti-HIV drug treatment earlier in pregnancy. But there are limited data on safety regarding some of the drugs. Your group did a study of one of the newer anti-HIV drugs, tenofovir, in pregnancy. Can you tell us about that study and what you've found?

Dr. Mofenson: Sure, and you've raised a very important point. Current recommendations for pregnant women call for administration of three anti-HIV drugs during pregnancy. But there are very limited safety data for some of these newer drugs, and NICHD has a special study called the Pediatric HIV/AIDS Cohort Study that's designed to look at the safety of these exposures in infants. And we enroll infants born to HIV-infected mothers and then follow the exposed but uninfected infants to look for any adverse effects. And in this study, we wanted to look at exposure to this drug called tenofovir, which can cause bad effects on the kidney and the bone. And we looked at over 2,000 uninfected children born to HIV-infected mothers, and tenofovir was used by 21 percent of the mothers while the rest of the children were exposed to other drugs. And the use of tenofovir by the pregnant women has increased over time from only 14 percent in 2003 to 43 percent in 2010. So we found no difference at birth in height, weight and size of the heads in the infants that were exposed to tenofovir compared to the other infants but we did find at age 1 year that infants exposed to tenofovir had grown slightly less in height and head circumference, and we're continuing to follow these children as well as we're going to be doing a special test to look at the amount of bone in the children over time to see whether this finding is significant or not. And I think this demonstrates the importance of us continuing to do research on potential side effects of these drugs. Even though the infant is uninfected, we want to be sure that there are no other side effects.

Dr. Guttmacher: Thank you, Lynne. Our second guest, Dr. Bill Kapogiannis, will talk about a study, which found that young men treated for HIV are at greater risk for low bone mass than men of similar age who are HIV-negative. Bill, tell us about the study, please.

Dr. Kapogiannis: Thank you, Allen. As you know, peak bone mass is achieved in adolescents and early adulthood, and this determines how strong your bones will be as an adult. The study we are talking about enrolled approximately 200 HIV-infected and 50 HIV-uninfected healthy young men between the ages of 14 and 25 years to see if there were associations between bone mass with HIV infection and with anti-HIV medications. Most participants identified as African American or Hispanic, and all lived in urban areas. The HIV-infected youth were diagnosed on average about 2 years earlier and were divided into two groups, those not receiving HIV medications and those who were. They had x-ray scans to measure their bone mass in certain regions of their bodies and answered questions about their medical history and diet, exercise, and other lifestyle habits. Young men being treated for HIV are more likely to have low bone mass than other men their age. For HIV-infected young men, on average, bone density in the hip was 5 to 8 percent lower and in the spine 2 to 4 percent lower than for study participants without HIV. Bone density and the calcium and other mineral content of bones tended to be the lowest in participants taking medication for HIV. So youth with HIV who had not begun treatment had higher bone mass levels than HIV-infected youth who were on anti-HIV medication, but lower bone mass levels than youth who did not have HIV. At least half of youth responded they did not take sufficient calcium or vitamin D. More than 30 percent smoked, half said that they did not get regular exercise, and so smoking and lack of exercise, as you know, can contribute to weaker bones. So what's the bottom line? The HIV-infected young men have been taking anti-HIV medications for a relatively short time since they were recently infected, yet they still had lower bone mass than others without infection their age. This means that if HIV medications impact bones, they do so relatively soon after they are started and at a crucial time when young men are still growing.

Dr. Guttmacher: Bill, you mention exercise and smoking. Do we know anything else about what might be causing the bone loss?

Dr. Kapogiannis: The study, Allan, was not designed to determine the cause of bone loss so it is difficult to pinpoint exactly and cannot rule out the possibility that low bone mass preceded the young men's HIV infection. But as you pointed out, all the young men had several risk factors for bone loss, such as tobacco smoke and alcohol use as well as low intake of calcium and vitamin D, which is needed to absorb calcium.

Dr. Guttmacher: So based on what we know at this point, is there anything that might be done to mitigate or reduce the rate of bone loss?

Dr. Kapogiannis: I think it would be a good idea for young men newly diagnosed with HIV to make sure they get exercise, get enough calcium and vitamin D, and quit smoking if they smoke, as well as limit alcohol consumption. Additionally, physicians who care for these patients should also consider monitoring them regularly for signs of bone thinning or low bone mass.

Dr. Mofenson: So, Bill, studies in adults with HIV have shown decreases in bone mineral density as well. What effect might such early bone loss have as these young men are aging?

Dr. Kapogiannis: Lynne, as you know, as people grow older, bones normally lose mass, and the earlier you start losing, the more net loss that accumulates with age, and they place people at greater risk for fractures later on in life. Additional studies are however needed to follow HIV-positive young men long term to determine whether bone loss during adolescence does in fact increase the risk of fractures later in life.

Dr. Guttmacher (Closing): Thank you, Bill. That brings us to the end of our podcast for this month. I'd like to thank Dr. Mofenson and Dr. Kapogiannis for joining us today and for sharing with us some of the HIV research that we are doing here at NICHD. I'd also like to thank our podcast listeners for joining us.

For more information on any of today's topics and many related topics, visit That's I'm Alan Guttmacher, and I hope you will join us for more NICHD podcasts as we post them on our Web site each month.

Announcer: This has been NICHD Research Perspectives, a monthly podcast series hosted by Dr. Alan Guttmacher. To listen to previous installments, visit If you have any questions or comments, please e-mail


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Last Reviewed: 11/30/2012
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