H A I spotlifall g ht2014 HARVARD SCHOOL OF PUBLIC HEALTH AIDS INITIATIVE photo by Kent Dayton Max Essex Q&A Infants & HIV ©iStock.com/MShep2 HEU Infants For over 20 years, the Harvard AIDS Initiative (HAI) has been conducting How Big and Bad Is the Problem? research on how best to care for mothers Imagine that you’re a young woman in with HIV, she was exposed to both HIV with HIV and their children. Martha southern Africa, giving birth to the child and ARVs in the womb. Henry, Editor of Spotlight, sat down with you’ve carried for nine months. Between Dr. Max Essex, Chair of HAI, to review the pain and the pushing, you feel both You learn that the term for babies like the progress made and the challenges excitement and dread. At the antenatal your daughter is HIV-Exposed Unin- remaining. clinic several months ago, you learned that fected (HEU) infants. And HEU infants HAI began working in Botswana you were infected with HIV. The doctor in resource-limited settings like southern in 1996. At that time, if a pregnant gave you antiretroviral (ARV) drugs to Africa are two to three times more likely woman was infected with HIV, what prevent your child from being born with to die within the first two years of life was the outlook for her and her child? HIV. You pray that they worked. than babies who weren’t exposed to HIV or ARVs. The health and survival of your ESSEX: In Africa in the late 1990s, little girl is still at risk. Researchers are Six weeks later, while your newborn the chances that an HIV-positive working urgently to understand why. sleeps in your arms, the clinic nurse gives woman would infect her infant in you the good news. Your daughter is not Aftereffects of Success utero or through birth or breastfeeding infected with HIV. You burst into tears was about 30 to 40%. At least one of relief and joy. But wait, not so fast. Figuring out how to prevent pregnant out of three babies born to HIV- Even though your baby isn’t infected HIV-infected women from passing the positive mothers would get infected. (continues on page 2) (continues on page 6) (continued from page 1) virus to their infants is one of the most inspiring success stories of the AIDS epidemic. From research done at the Harvard AIDS Initiative (HAI) and elsewhere, we have learned how to reduce mother-to-child transmission rates from 30–45% without ARVS down to as low as 1% with ARVs in resource-limited settings, even when a mother breastfeeds her infant. In 2010, the World Health Organiza- tion (WHO) endorsed the bold goal of eliminating mother-to-child transmis- sion of HIV by 2015. With both scien- tists and health policy experts focused on preventing new infant infections, there Dr. Kate Powis, photo by Kent Dayton had been an assumption that ensuring “There’s a growing sense of urgency are often exposed to illness, death, and that a baby remained HIV-free would because we’ve only begun to appreciate family disruptions at a young age. safeguard the child’s survival. the magnitude of this problem,” said Dr. Max Essex, Chair of HAI. “Bear in mind The increased mortality of HEU in- “It is estimated that there are approxi- that until five or ten years ago, most at- fants is predominantly due to deaths mately 1.5 million HIV+ pregnant wom- risk infants weren’t even protected from from infectious diseases, namely compli- en annually,” said Dr. Elaine Abrams, a HIV infection.” cations of pneumonia and diarrhea. It is professor of epidemiology and pediatrics an open question whether these deaths at Columbia University and an expert on Many Factors that stem from immunological problems mother-infant HIV transmission. “With or from the disadvantages of being born successful prevention programs, we can Researchers at HAI are looking close- into an HIV-affected household. It is hope to see HIV transmission rates as ly at how and why HEU infants differ likely a combination of both. low as 2–5% and perhaps as many as one from infants who were never exposed to million HEU infants born each year.” HIV and ARVs. The difference is likely Growth Problems a combination of biological, social, and Fewer and fewer infants born to in- economic factors. “This is a complicated Growth is a good indicator of over- fected mothers became infected with question that requires thoughtful, cre- all infant health. The first 1000 days of HIV. That’s wonderful news. But with ative research,” said Essex. life are the most critical time for growth the number of HEU newborns surpass- and affects a person’s entire lifetime. ing a million each year, we must look The health of a mother is critical to Some researchers have found that HEU closely at the health of these still-vulner- the health of her child. The womb of infants are more likely to have stunted able children. An increasing body of evi- an HIV-infected woman taking ARVs growth, lagging behind in both weight dence suggests that HEU babies are not is different from that of an HIV-free and length. like babies who have never been exposed woman. Recent studies have found that to HIV. It’s a problem we’re just begin- some HEU infants fail to get a healthy “Growth is a kind of a barometer of ning to understand. immune system because the mother’s how sturdy you’re going to be if you get immune system is compromised. sick early in life,” said Dr. Kate Powis, an “With increasing success of preven- HAI researcher whose work focuses on tion efforts, the clinical and research Many HIV-infected mothers, besides improving the health of HEU infants. community are shifting attention to dealing with their own disease, tend to “Children who have lower weight or HEU and only now beginning to delin- be more impoverished. They tend to length for age face a higher risk of mor- eate the particular health issues of this have less access to a toilet and clean wa- tality. If they get diarrhea or pneumonia, growing, highly vulnerable population,” ter in the home. Because HEU infants they’re more likely to need hospitaliza- said Abrams. live in a household affected by HIV, they tion or to die.” 2 Building on Experience Along with Essex, Drs. Shahin Lock- man and Roger Shapiro have been con- ducting PMTCT research at the BHP for more than a decade. The landmark Mashi and Mma Bana clinical trials made important contributions to PMTCT re- search. The data from those trials will help Powis conduct a retrospective analy- ses of 1,930 women and their infants to look at the impact of giving mothers one drug versus a triple-drug cocktail and how that affects the health and growth of a developing child. In new research, Shapiro is following children in Botswana from birth through two years of life to try to better under- Understanding why HEU infants HAI researchers have achieved in clinical stand infant mortality. Lockman is look- have stunted growth and finding a so- trials. However, in the coming years, up ing at the neurodevelopmental outcomes lution is of utmost concern, especially to 30% of all infants born in Botswana and mortality of HEU children com- in southern Africa, the epicenter of the will be born HIV Exposed Uninfected pared to unexposed children and children HIV/AIDS epidemic. (HEU). with HIV. In another study, Lockman and Shapiro are testing whether giving a What HAI Is Doing low-cost antibiotic called co-trimoxazole To address the needs of this growing will help protect against death, diarrhea HAI is a leader in HEU research. As group of children, HAI researchers and pneumonia in nearly 3,000 HEU Max Essex explains, “We’ve got people are asking a number of important children. Powis is hoping to launch an who know a lot about mother-to-infant questions: innovative study that compares the gut transmission: how and why that occurs microbiome of HEU infants with unex- and how to prevent it. We also have 1. What are the safest drugs to posed infants to learn more about differ- people who know a lot about the immu- prevent mother-to-child transmission ences in the development of the immune nology of human resistance to HIV in- of HIV for both the mother and the system. fection and why it does or doesn’t work. developing infant? A lot of that information is useful in de- 2. Which respiratory and gastro- Time to Act termining what sort of mechanisms are intestinal infections cause the most compromised in children who didn’t get problems for HEU infants? The success of WHO-sanctioned infected with HIV but are still at high ARV treatment and PMTCT programs 3. Can we lower the risk of HEU will continue to increase the prevalence risk for all these other conditions.” babies dying from infectious diseases by giving them a widely available of HEUs. This is of particular impor- In the African country of Botswana, antibiotic during their most vulnerable tance in southern Africa, where HEUs where HAI has been working since 1996, first 1–2 years of life? may represent up to 30% of infants born approximately 30% of pregnant women in areas with a high HIV prevalence. are infected with HIV. Botswana’s 4. What is the impact of HIV exposure versus ARV exposure? What is becoming increasingly clear is Prevention of Mother-to-Child-Trans- that just keeping a baby HIV-free is in- mission (PMTCT) program is the most 5.