This February marks the 20th anniversary of the results of Pediatric AIDS Clinical Trials Group Protocol 076—the first study to show that drug therapy could reduce the risk of mother-to-child transmission of HIV/AIDS. The NICHD and the National Institute of Allergy and Infectious Diseases (NIAID) co-funded this study.
On February 18, 1994, the study's data safety monitoring board stopped the trial because the drug's effects were so dramatically positive. The study demonstrated a two-thirds reduction in the risk of infant HIV infection by giving the antiretroviral drug zidovudine to women before and during childbirth and to the infant after birth.1 Rapid implementation of the drug regimen used in the study quickly reduced mother-to-child transmission rates in the United States from 25% or more to around 8% within about 2 years.1
Today in the United States, fewer than 200 children a year are born with HIV.2 Mother-to-child transmission (MTCT) rates are only about 1% with appropriate use of today's even more effective drug regimens.3
The NICHD has built on this early success and continues to support research on the prevention of MTCT (PMTCT) of HIV and other infections. Select a link below to find out more.
A New HIV Initiative for Low-resource Settings Ongoing HIV Prevention Efforts Studies of HIV-associated Co-infections and Other Conditions
The United States and other resource-rich countries have seen significant decreases in rates of MTCT of HIV, but much remains to be done in resource-limited parts of the world. In sub-Saharan Africa, for example, approximately 1.28 million pregnant women and 2.9 million children live with HIV.4 Death rates for infants and toddlers born with HIV who don't receive treatment remain high. And even though MTCT rates have fallen significantly there in recent years, in 2012, 230,000—or over 88%—of the 260,000 children worldwide newly infected with HIV through MTCT were in sub-Saharan Africa.5
To help address this public health problem, the NICHD has committed $21.5 million over 5 years, with the United States President's Emergency Plan for AIDS Relief (PEPFAR) contributing an additional $2 million, to support eight new research grants. The objective of these grant projects is to evaluate the safety and effectiveness of triple-antiretroviral drug treatments in reducing MTCT of HIV in resource-constrained settings.
The new initiative is a response to the evolving nature of HIV/AIDS infections and advances in treatments that are often slow to reach resource-constrained countries. Treatment guidelines set forth by the World Health Organization offer both a useful starting point and additional research questions:
For more information about this grant program, see FOA RFA-HD-14-027: Safety and Effectiveness of Triple Antiretoviral Drug Strategies for Prevention of Mother to Child HIV Transmission.
The PROMISE (Promoting Maternal-Infant Survival Everywhere) Study, co-funded by the NICHD and the NIAID through the International Maternal, Pediatric, Adolescent AIDS Clinical Trials (IMPAACT) Network, is looking at the safety and efficacy of PMTCT interventions in both breastfeeding and formula-feeding infants. The study addresses the following questions:
Enrollment of mother-child pairs is ongoing at a wide variety of sites. These include locations in numerous countries in sub-Saharan Africa and sites in Argentina, Brazil, India, China, Thailand, and the United States. To date, more than 3,000 HIV-infected mothers have been enrolled during pregnancy and approximately 2,000 mother-child pairs are being followed during the breastfeeding period.
The PEPFAR Implementation Science Awards for PMTCT are jointly funded by the NICHD and other NIH Institutes and Centers, in collaboration with the Office of the U.S. Global AIDS Coordinator. Implementation science is the study of ways to translate research findings into both practice and health care policy. The NICHD and PEPFAR awarded nine grants through this program in fiscal year 2012, for a total of $7.8 million over the 2-year grant period.
These projects will address such topics as:
These implementation science studies link directly to programs, researchers, and institutions in seven countries receiving PEPFAR support. The Center for Global Health Studies at NIH's Fogarty International Center organizes bi-annual meetings to serve as a forum for researchers, key collaborators, and the PMTCT implementers in PEPFAR projects to exchange information as this new research progresses.
For more information on this grant program, see FOA RFA-HD-12-210: NIH/PEPFAR Collaboration for Advancing Implementation Science in PMTCT.
The NICHD-funded Prevention of Malaria and Improving HIV Outcomes in Tororo, Uganda, (PROMOTE) is a collaborative research project by investigators at the University of California, San Francisco, and at Makerere University in Uganda that focuses on the intersection of HIV and malaria in pregnant women and in children. HIV-infected individuals have higher malaria infection rates and more severe malaria episodes. In sub-Saharan Africa, with about 25 million people living with HIV infection,6 there are an estimated 165 million cases of falciparum malaria each year.7 Pregnant women have 3 times the risk of severe malaria, with a death rate of nearly 50%.8 Severe malaria in pregnancy also affects infant outcomes, including a high risk of congenital malaria, with higher rates of low birth weight, prematurity, fetal distress, and death. Some studies have suggested increased rates of MTCT of HIV associated with maternal malaria.9
PROMOTE I, the initial 5-year project, included three randomized clinical trials to test the effectiveness of different therapies in decreasing the number of malaria infections and the severity of illness due to malaria.
PROMOTE I also included an evaluation of the nutritional status of all program participants and a study of malaria parasite drug resistance.
PROMOTE II builds on the results of the project's first phase. The new study will evaluate prevention of malaria in pregnant women, including both HIV-infected and uninfected women, and their infants. Researchers will compare the standard recommended preventive treatment to a new combination regimen (dihydroartemisinin-piperaquine) shown to be highly effective and safe for pregnant women and children.
In sub-Saharan Africa, tuberculosis continues to be the leading cause of death among people with HIV. A pregnant woman living with HIV has a 10 times higher risk of developing active tuberculosis than a pregnant woman without HIV.12 Moreover, tuberculosis is associated with more than double the risk of MTCT of HIV before birth.
In an ongoing study in South Africa supported by NICHD, researchers are looking at how tuberculosis-HIV co-infection in pregnant women affects maternal and fetal outcomes. Because treatment for tuberculosis during pregnancy can interfere with HIV treatment, the study will also assess the impact of tuberculosis treatment on the levels of anti-HIV drugs in these co-infected women. For more information, visit Impact of Tuberculosis on Outcome of HIV in Pregnant Women.
Another study, conducted by the NICHD- and NIAID-funded IMPAACT Network, is evaluating the efficacy and safety of the anti-tuberculosis drug isoniazid for prevention of tuberculosis in HIV-infected women. Researchers are testing the use of the drug in women who receive it during pregnancy and in those who wait until the postpartum period.
Other ongoing studies focus on MTCT of hepatitis, independent of HIV status. In one study, Antiviral Prophylaxis to Prevent Perinatal Transmission of Hepatitis B Virus in Thailand, researchers are testing the effectiveness of an experimental treatment with an anti-hepatitis B drug called tenofovir. Mothers receive the drug during pregnancy, and infants receive the standard therapy of immunoglobulin at birth, followed by a subsequent hepatitis B vaccine.
In the ongoing study An Observational Study of Hepatitis C Virus in Pregnancy, researchers are seeking to better understand the risk factors for passing the hepatitis C virus from mother to child.
Whether focused on HIV, malaria, tuberculosis, or hepatitis, NICHD researchers continue to make significant progress toward the goals of eliminating prenatal and infant infections and improving the health and well-being of mothers and infants worldwide.
For more information on this topic, select one of the following links:
Originally Posted: February 18, 2014
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