To commemorate the 30th anniversary of the first reported cases of AIDS, the NICHD highlights some key moments in pediatric, adolescent, and maternal AIDS research
Figure 1: Thin-section transmission electron micrograph depiction of structural details of a number of HIV virus particles. Image courtesy of the Public Health Image Library; credit to Dr. A. Harrison & Dr. P. Feorino.
As scientific understanding of the disease and its mechanisms continues to advance, we can find reasons to hope. Where once there were no treatment options, we now have multiple regimens that can help to manage the disease. Where once the disease spread seemingly without boundaries, we now have ways to prevent that spread. Researchers, health care providers, and communities around the world remain dedicated to preventing, treating, managing, and even curing AIDS.
During the last 30 years, the NICHD and its researchers have played important roles in improving the outlook for children, adolescents, women, and mothers who have or are at risk for AIDS. While keeping in mind the many challenges that remain, the NICHD highlights some of the key moments in the history of AIDS/HIV, specifically related to children, adolescents, women, and mothers. No single list of a 30-year span can be all inclusive, but these highlights provide a good overall picture of how far we've come, and how far we still have to go.
Select a period below to view the research highlights for that timeframe.
1981 to 1985
The Centers for Disease Control and Prevention (CDC) publishes the first reports of AIDS, although identified by another name, in the Morbidity and Mortality Weekly Report ( MMWR). The reports describe cases of Pneumocystis pneumonia and Kaposi's sarcoma in 41 otherwise healthy homosexual men. The reports appear in the June MMWR and July MMWR.
Three notable reports appear in the MMWR. The first describes cases of Pneumocystis pneumonia among patients with hemophilia A . The second details four infants with unexplained cellular immunodeficiency and opportunistic infections similar to those reported in adults. Of the four infants, three were born to mothers with then-identified risk factors for AIDS, while the other received a blood transfusion from a patient with AIDS. The authors note that "transmission of an 'AIDS agent' from mother to child, either in utero or shortly after birth, could account for the early onset of immunodeficiency in these infants." The third describes similar cases of immunodeficiency in patients with hemophilia A, including a 10-year-old boy.
1986 to 1990
The NICHDestablishes the Mother and Infants Cohort Study (MICS) at five study sites in the New York boroughs of Brooklyn and the Bronx, which had nearly one-half of all perinatally acquired AIDS cases at the time. The study is a collaboration between the NICHD and the National Cancer Institute (NCI). Researchers aim to evaluate factors associated with mother-to-child HIV transmission, how HIV affects pregnancy and pregnancy outcomes, how pregnancy alters the progression of HIV infection, and how it affects infant growth and neurodevelopment.
The U.S. Food and Drug Administration (FDA) approves AZT as the first antiretroviral drug for the treatment for AIDS in adults; use in children is not approved at this time.
- The NICHDestablishes the Hemophilia Growth and Development Study, an investigation of the impact of HIV infection on physical growth and sexual maturation, immune function, and neurological and psychological development in children and adolescents with hemophilia. Researchers enroll 333 children and adolescents (6 to 19 years old) at 14 U.S. hemophilia treatment centers between 1988 and 1997.
- The NICHD establishes the Pediatric, Adolescent, and Maternal AIDS Branch to support and conduct epidemiologic, biomedical, and bio-behavioral research in the areas of HIV/AIDS in mothers, women of reproductive age, infants, children, adolescents, and families.
- The NICHD Intravenous Immunoglobulin (IVIG) Study Group starts enrolling patients into the first randomized Phase III clinical trial to evaluate whether IVIG can effectively prevent serious bacterial infections in HIV-infected children—the first clinical trial conducted in HIV-infected children in the United States. This study group later becomes the NICHD Domestic and International Pediatric and Perinatal HIV Clinical Trials Network, a primary resource for clinical studies on preventing and treating HIV infection and its complications in newborns, infants, children, adolescents, and pregnant women.
- The NICHD and the National Institute of Allergy and Infectious Diseases (NIAID) initiate the Women and Infants Transmission Study (WITS), a study of HIV transmission during pregnancy and birth.
- Researchers at the NCI report the first studies of an antiretroviral drug in children. They show that continuous intravenous infusion of AZT can reverse severe neurocognitive deficits in children with HIV infection.
1991 to 1995
- In a collaboration between the NIAID, the NICHD, and the Agence Nationale de Recherche sur le Sida (ANRS) in France, researchers begin enrolling pregnant women in the United States and France in the first studies (called ACTG 076) to examine AZT for the prevention of mother-to-child HIV transmission in pregnancy, during labor, and after birth.
- IVIG Study Group researchers report in the New England Journal of Medicine that the use of IVIG to prevent serious bacterial infections reduces the infection risk in children with HIV who are not receiving antiretroviral drugs.
- The FDA approves IVIG for use in HIV-infected children (a new indication) to decrease the frequency of bacterial infections, increase the time free from serious bacterial infections, and decrease the frequency of hospitalizations.
- The FDA approves didanosine, as the second antiretroviral drug approved for treatment of HIV infection, and was approved concurrently for adults and children.
- The Data and Safety Monitoring Board of the NIAID-/NICHD-/ANRS-funded clinical trial examining whether AZT can prevent mother-to-child transmission of HIV (ACTG 076) halts the study early because results indicate that the AZT regimen is significantly more effective than placebo at preventing transmission. Findings indicate that mother-to-child transmission of HIV is reduced by two-thirds if women are treated with AZT during pregnancy and labor, and if newborns are given AZT for six weeks. Results, published in the New England Journal of Medicine, rapidly become the standard of care for HIV-infected pregnant women and infants in the United States.
- The FDA approves new labeling for AZT, adding "prevention of HIV transmission from infected pregnant women to their children during pregnancy, in labor, and after birth."
- The U.S. Public Health Service and the U.S. Department of Health and Human Services (DHHS) issue guidelines on the use of AZT to prevent mother-to-child HIV transmission in the United States.
- The NICHD establishes the Adolescent Medicine HIV/AIDS Research Network (AMHARN). Studies conducted through the network focus on adolescents (ages 12 years to 19 years) who became infected with HIV from sex or drug-taking. The studies investigate medical, behavioral, and psychological aspects of HIV/AIDS in these adolescents. The ultimate goal of this project is to improve the care of HIV-infected adolescents based on a better understanding of the progression of HIV and of other diseases that often accompany HIV infection in adolescents.
- The ACTG splits into two separate programs, the Adult ACTG and the Pediatric ACTG (PACTG), establishing a clinical trials group focused on HIV in children and pregnant women. The PACTG collaborates with the NICHD's Domestic and International Pediatric and Perinatal HIV Clinical Trials Network in the conduct of pediatric and perinatal trials.
- The NCI launches the first studies in children of a new class of antiretroviral drugs, protease inhibitors. A study of the protease inhibitor ritonavir starts in June ( published in March 1998 in Pediatrics), followed by a study of indinavir in July ( published in July 1998 in Pediatrics).
- The CDC issues guidelines for HIV testing in pregnancy. For the first time in the United States, routine HIV counseling and voluntary testing are recommended for all pregnant women. These recommendations are based on the results of the NIAID-/NICHD-/ANRS-funded clinical trial (ACTG 076), which demonstrated that AZT prevented mother-to-child HIV transmission.
- Sites in the NIAID/NICHD-funded PACTG and the NICHD Domestic and International Pediatric and Perinatal HIV Clinical Trials Network launch studies of nevirapine, one of a new class of antiretroviral drugs called non-nucleoside reverse transcriptase inhibitors, in children. The drug is later approved for treating children based on the results of these studies, published in the Journal of Infectious Diseases in 1996 .
- FDA approves lamivudine (3TC) for use in combination with AZT concurrently in adults and children.
1996 to 2000
- The FDA grants accelerated approval for nelfinavir concurrently in adults and children, making it the first protease inhibitor labeled for use in children. The FDA also approves pediatric labeling for the protease inhibitor ritonavir, one year after approving the drug for use in adults.
- NIAID/NICHD-funded researchers from WITS describe the dynamics of HIV replication in infants who become infected with HIV in the womb, during labor, or shortly after birth. The researchers show that HIV replication in these infants differs significantly from HIV replication observed in adults. Researchers from the NICHD IVIG Study Group also demonstrate that HIV RNA levels (viral load) and CD4 cell counts each can effectively predict whether an HIV-infected child will survive.
- NIAID/NICHD-fundedPACTGresearchers report on a clinical trial demonstrating that didanosine or a combination of didanosine and AZT is a safe and effective treatment option for HIV-infected children. The findings appear in the New England Journal of Medicine.
- Researchers release preliminary results from another PACTG clinical trial demonstrating that therapy with two drugs (AZT/lamivudine or AZT/didanosine) better protects HIV-infected children from progressive illness and death than does single-drug therapy. Researchers publish their results in the Journal of Pediatrics in 1998 .
- The HIV Prevention Trials Network (HPTN) reports findings from a study of nearly 7,000 pregnant women in Blantyre, Malawi, showing that cleaning the birth canal with an inexpensive antiseptic solution reduces post-birth bacterial infections, but does not reduce HIV transmission from mother to child. The HPTN conducts the study with funding from NIAID, NICHD, and the National Institute of Mental Health (NIMH).
- PACTG sites launch studies of a new drug, efavirenz, as part of a cocktail to treat HIV infection in children. The FDA later approves the drug for use in adults and children in 1998.
- The NICHD-funded Domestic and International Pediatric and Perinatal HIV Clinical Trials Network reports the results of a study of more than 8,500 mother-infant pairs that showed HIV-infected pregnant women who deliver by cesarean section had a 50-percent lower risk of transmitting HIV to their infants. Shortly thereafter, the DHHS guidelines for the prevention of mother-to-child transmission are modified to recommend elective cesarean section for HIV-infected pregnant women with HIV RNA level greater than 1,000 near the time of delivery based on the study findings.
- Results from an NICHD-funded study demonstrate that hyperimmune HIV immunoglobulin is no more effective at preventing mother-to-child HIV transmission than is AZT alone. Results also show that AZT is as effective in women with severe immune deficiency as it is in women with higher white blood cell counts.
- FDA approves amprenavir for treatment of HIV with concurrent approval for both children and adults.
- The CDC estimates that in the United States, the number of cases of AIDS contracted before, during, or shortly after birth peaked in 1992. The number of infants who contracted AIDS in the first year of life declined 80 percent between 1992 and 1997, coinciding with a significant increase in HIV testing for pregnant women and in the use of AZT to prevent transmission from HIV-infected pregnant women to their infants.
- Investigators report that the amount of HIV in a pregnant woman's blood (also called viral load) is the primary risk factor in transmitting the virus to infants. The findings, from the NICHD-funded PACTG study and the NIAID/NICHD-funded WITS study, appear in the same issue of the New England Journal of Medicine.
- Early results from one of the NIH-funded HIV Network for Prevention Trials (HIVNET) study in Uganda show that giving a single dose of nevirapine to mothers in labor and to their infants at birth can reduce mother-to-infant transmission of HIV during birth by 50 percent. This regimen is slightly less effective than the regiment used in the NIAID-/NICHD-/ANRS-funded clinical trial (ACTG 076). However, because it is simple to administer and affordable, this intervention becomes important for countries that can't afford the long course of AZT used in wealthier countries.
2001 to 2005
- Researchers with the NIH-funded HIVNET trial in Kampala, Uganda, report that some mothers and infants who receive single-dose nevirapine to prevent the transmission of HIV during birth developed viral mutations conferring resistance to nevirapine.
- The NICHD establishes a multi-center research network, called the Adolescent Trials Network for HIV/AIDS Interventions (ATN), to study treatments for HIV infection among adolescents in the United States after the AMHARN External Scientific Advisory Panel identifies the need for such a network. The mission of the ATN is to conduct a broad array of intervention studies aimed at the primary, secondary, and tertiary prevention of HIV infection in pre-adolescents, adolescents, and young adults (through age 24 years) at clinical sites and in the surrounding communities.
- The CDC issues revised recommendations for HIV testing during pregnancy in the United States. The revised guidelines emphasize HIV testing as a routine part of prenatal care, recommend simplifying the consent process, and endorse testing during labor and delivery for women who have not received prenatal HIV testing.
The FDA approves the injectable HIV drug enfuvirtide, the first of a new class of antiretrovirals called fusion inhibitors. The drug is approved concurrently for HIV-infected adults and children older than age 6 years, based on studies performed by PACTG.
- The FDA approves use of emtricitabine (FTC) for treatment of HIV infection in children two years after it is approved in adults.
- The NICHD establishes the Pediatric HIV/AIDS Cohort Study (PHACS) to address two crucial issues in pediatric HIV research: the long-term safety of fetal and infant exposure to preventive antiretroviral chemotherapy, and the effects of perinatally acquired HIV infection and its treatment in U.S. adolescents. In addition to the NICHD, the initiative received support from NIAID; the National Heart, Lung, and Blood Institute; NIMH; NIDA; the National Institute on Deafness and Other Communication Disorders; the National Institute of Neurological Disorders and Stroke; and the National Institute on Alcohol Abuse and Alcoholism.
- NIAID establishes the International Epidemiologic Databases to Evaluate AIDS (IeDEA), and the NICHD begins funding the pediatric component of the IeDEA. The initiative supports seven regional data centers, which bring together clinical and research data resources to answer questions about HIV/AIDS that single studies are too small to answer. By 2011, the database includes data on more than 50,000 HIV-infected children who live in resource-limited areas.
2006 to 2011
- Researchers from the NICHD/NIAID/NIMH-funded PACTG report that death rates of children with HIV have decreased more than nine-fold since the use of Highly Active Antiretroviral Therapy (HAART) in the mid-1990s. In spite of this improvement, the findings show the rate of death among young people with HIV still is 30 times that among young people who do not have HIV.
- The NICHD, NIAID, and NIMH collaborate to initiate the PROMISE (Promoting Maternal–Infant Survival Everywhere) study in the IMPAACT group. PROMISE aims to enroll 6,000 HIV-infected mothers and their infants to examine the best ways to prevent mother-to-child HIV transmission, optimize maternal health outcomes, and maximize infant survival.
- ThePresident's Emergency Plan for Treatment of AIDS (PEPFAR) publishes Prevention of Mother-to-Child Transmission of HIV: Expert Panel Report and Recommendations to the U.S. Congress and U.S. Global AIDS Coordinator (PDF - 1.2 MB), describing interventions in developing countries supported by PEPFAR.
- FDA approves tenofovir for use in treating in HIV-infected children ages 12 years to 18 years; the decision comes nine years after it was approved for adults.
- Separate studies published simultaneously in the New England Journal of Medicine show that giving a triple antiretroviral drug regimen to HIV-infected breastfeeding women (who don't need therapy for their own health) and daily administration of nevirapine to breastfeeding infants each significantly reduces the risk of HIV transmission through breastmilk. The NIAID-funded Mma Bana study in Botswana and the CDC-funded Breastfeeding and Nutrition study in Malawi show that both interventions appear to be safe and effective, adding to the available treatment options for breastfeeding women.
- WHO publishes revised guidelines for the treatment of adults, pregnant women, and children with antiretroviral drugs (PDF - 1.15 MB), for HIV and infant feeding (PDF - 1.57 MB), and for treatment of infants and children with antiretroviral drugs (PDF - 1.89 MB). The guidelines recommend treatment for all HIV-infected infants younger than age 2 years.
- Researchers in the IMPAACT group report that protease inhibitor-based therapy with a combination of lopinavir/ritonavir is a better treatment for HIV-infected children who are exposed to nevirapine at birth than is nevirapine-based therapy. A related finding from the same study group finds that lopinavir/ritonavir-based therapy is also a better treatment for HIV-infected children who were not exposed to nevirapine at birth than is nevirapine-based treatments . These data demonstrate that protease inhibitor treatment is better for all young children, whether they have been exposed to single-dose nevirapine or not.
For more information on NICHD-supported research on HIV/AIDS, select a link below:
Originally posted: June 3, 2011
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