Study Tracks Children Exposed to HIV Before Birth
Prior to 1994, 25% to 35% of infants born to HIV-positive mothers became HIV positive themselves. But a landmark NICHD-led study1 published that year showed that the risk of mother-to-child transmission could be greatly reduced with antiretroviral therapy (ART).
Children of HIV-infected mothers are now routinely given a course of ART perinatally (while they are still in the womb or shortly after birth) and most of these children now avoid infection.
Although reducing these numbers is a major accomplishment and public health advance, research continues to ensure ART is the best it can be and that those who receive the treatment remain healthy. The NICHD and other NIH Institutes continue to make this research a priority through the Pediatric HIV/AIDS Cohort Study (PHACS). To learn more about some of the Study's findings, select a link below.
Long-Term PHACS Studies
In 2005, as the first children to receive ART moved toward adolescence, the NICHD and other NIH Institutes launched PHACS to get more information about the health of these children over time. In particular, PHACS studies aim to:
- Understand how HIV and its treatment affect growth and development, sexual maturation, organ function, and socialization of perinatally HIV-infected pre-adolescents, adolescents, and young adults.
- Acquire more information on the long-term safety of ART when used during pregnancy and in newborns.
- Ensure there is a way to estimate the upper bounds of risk for children who were exposed to ART during maternal treatment to prevent perinatal HIV transmission.
- Continue the follow-up study of these populations.
PHACS is funded by the NICHD through the Maternal and Pediatric Infectious Disease Branch and by several other NIH Institutes.
Long-Term PHACS Studies
Currently, PHACS supports two multicenter studies that began in 2007 and will continue at least until 2015.
- Surveillance Monitoring for ART Toxicities Study in HIV-Uninfected Children Born to HIV-Infected Women (SMARTT) will enroll up to 3,400 children who were born to HIV-infected mothers but who are uninfected themselves. (The child need not have received ART to be eligible for enrollment.) The study initially enrolled 1,240 children, all younger than 12 years of age, and continues to enroll up to 300 newborns per year. The study is designed to understand health outcomes among children exposed to ART. Among outcomes the study examines are abnormalities of the heart, growth problems, and delays in language and intellectual development. You can learn more about SMARTT at http://clinicaltrials.gov/ct2/show/NCT01310023.
- Adolescent Master Protocol (AMP) is examining the impact of HIV infection and ART on nearly 700 pre-adolescents and adolescents who acquired the infection from their mothers. The study includes a control group of children who were born to HIV-infected mothers, but who are not infected. Children had to be at least 7 years old and no older than 16 years to enroll in the study. Among other things, AMP will assess the impact of HIV infection and ART on growth, sexual maturation, heart function, bone health, and cognitive, academic, and social development. The study will also identify the toxic effects, if any, of ART. Learn more about the AMP at http://clinicaltrials.gov/show/NCT01418014.
Both SMARTT and AMP have provided and continue to provide important information, including some long-term health outcomes of perinatal HIV infection and exposure.
Among the findings so far are the following:
- Perinatally HIV-infected children and adolescents born more recently (1994–2002) had higher CD4 counts (signifying a healthier immune system) and better HIV control than those born earlier (1991–1993).2
- Among perinatally HIV-infected youth, 15% had insulin resistance, although it may be linked to obesity more than to ART and HIV.3 With insulin resistance, the body makes insulin but does not use it effectively. As a result, glucose builds up in the blood, leading to type 2 diabetes or prediabetes.
- Asthma and atopic dermatitis (a skin condition also called eczema) are more common in perinatally HIV-infected children and adolescents compared to perinatally HIV-exposed but uninfected children and adolescents.4
- Compared to children from the general population, hearing loss is more common in children who were exposed perinatally to HIV.5
- Combination ART protects against heart problems in perinatally HIV-infected youth.6
- Both HIV-exposed but uninfected and HIV-infected youth have high risk of language impairment.7 However, more recent research indicates that the risk is not associated with the antiretroviral therapy.8 Children exposed to HIV in the womb and whose mothers received combinations of anti-HIV drugs during pregnancy were no more likely to have language delays than were children exposed to HIV in the womb and whose mothers did not receive these recommended treatments.
- Perinatally HIV-infected youth enter puberty slightly later compared to perinatally HIV-exposed but uninfected youth. However, it seems that current ART treatment, as opposed to what was in use from 1991–1993, may result in more normal timing of puberty.9
- Both HIV-exposed but uninfected children and adolescents had a higher rate of mental health problems than did HIV-infected children and adolescents.10
Some PHACS studies have also looked at behavioral outcomes among study participants. Among the results reported from those studies are:
- Among sexually active, perinatally HIV-infected youth, 62% reported having unprotected sex. Among those who had unprotected sex, 42% had detectable levels of HIV in their blood. Among the youth with detectable levels of HIV, 22% had a form of the virus that was resistant to multiple classes of AIDS drugs.11
- Among a subset of sexually active, perinatally HIV-infected youth, roughly 20% reported that they did not know their HIV status the first time they had sexual intercourse.11
- Illicit substance use during pregnancy among HIV-infected women was low and was substantially less than the women in earlier studies.12
Other PHACS studies have looked at treatments. One such study found that the antiretroviral drug tenofovir was used by almost 40% of HIV-infected women during pregnancy.13 (The use of tenofovir continues to increase and is now about 60%.)
Collaboration and data sharing are also critical to PHACS and will lead to better treatments not only for HIV/AIDS, but also for other infections and health conditions. For example, a collaboration between PHACS and the Centers for Disease Control and Prevention led to the recommendation from the Advisory Committee on Immunization Practices that HIV-infected youth be re-immunized for measles after receiving combination ART.
PHACS has identified health issues associated with perinatal exposure to HIV, as well as positive health outcomes of ART. The effort to increase knowledge continues with SMAART and AMP, with the aim of evaluating better treatments, more targeted preventive efforts, and more timely care.
For more information about PHACS, select one of the following links:
Originally Posted: August 2, 2013
All NICHD Spotlights
- Connor, E. M., Sperling, R. S., Gelber, R., Kiselev, P., Scott, G., O'Sullivan, M. J., . . . Balsey, J. (1994). Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. New England Journal of Medicine, 331. 1173–1180.
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- Van Dyke, R. B., Patel, K., Siberry, G. K., Burchett, S. K., Spector, S. A., Chernoff, M. C., . . . Seage, G. R, III. (2011). Antiretroviral treatment of U.S. children with perinatally acquired HIV infection: Temporal changes in therapy between 1991 and 2009 and predictors of immunologic and virologic outcomes. Journal of Acquired Immune Deficiency Syndrome, 57(2), 165–173. PMID: 21407086 [top]
- Geffner, M. E, Patel K, Miller TL, Hazra R, Silio M, Van Dyke RB, Borkowsky W, Worrell C, DiMeglio LA, Jacobson DL. (2011). factors associated with insulin resistance among children and adolescents perinatally infected with HIV-1 in the Pediatric HIV/AIDS Cohort Study. Hormone Research in Paediatrics, 76, 386–391. PMID: 22042056 [top]
- Siberry, G. K., Leister, E., Jacobson, D. L., Foster, S. B., Seage, G. R., III, Lipshultz, S. E., . . . Shearer, W. T. (2012). Increased risk of asthma and atopic dermatitis in perinatally HIV-infected children and adolescents. Clinical Immunology, 142(2), 201–208. PMID: 22094294 [top]
- Torre, P., III, Zeldow, B., Hoffman, H. J., Buchanan, A., Siberry, G. K., Rice, M., . . . Williams, P. L. (2012). Hearing loss in perinatally HIV-infected and HIV-exposed but uninfected children and adolescents. The Pediatric Infectious Disease Journal, 31(8), 835–841. PMID: 22549437 [top]
- Lipshultz, S. E., Williams, P. L., Wilkinson, J. D., Leister, E. C., Van Dyke, R. B., Shearer, W. T., . . . Colan, S. D. (2013). Cardiac status of children infected with human immunodeficiency virus who are receiving long-term combination antiretroviral therapy: Results from the Adolescent Master Protocol of the Multicenter Pediatric HIV/AIDS Cohort Study. JAMA Pediatrics, 167(6), 520–527. PMID: 23608879 [top]
- Rice, M. L., Buchanan, A. L., Siberry, G. K., Malee, K. M., Zeldow, B., Frederick, T., . . . Williams, P. L. (2012). Language impairment in children perinatally infected with HIV compared to children who were HIV-exposed and uninfected. Journal of Developmental and Behavioral Pediatrics, 33(2):112–123. PMID: 22179050 [top]
- https://www.nichd.nih.gov/news/releases/Pages/071813-hiv_language_delays.aspx [top]
- Williams, P. L., Abzug, M. J., Jacobson, D. L., Wang, J., Van Dyke R. B., Hazra, R., . . . Geffner, M. E. (2013). Pubertal onset in children with perinatal HIV infection in the era of combination antiretroviral treatment. AIDS, 27(12) 1959–1970. [top]
- Malee, K. M., Tassiopoulos, K., Huo, Y., Siberry, G., Williams, P. L., Hazra, R., . . . Mellins, C. A. (2011). Mental health functioning among children and adolescents with perinatal HIV infection and perinatal HIV exposure. AIDS Care, 12, 1533–1544. PMID: 21702707 [top]
- Tassiopoulos, K., Moscicki, A. B., Mellins, C., Kacanek, D., Malee, K., Allison, S., . . . Seage, G. R. (2013). Sexual risk behavior among youth with perinatal HIV infection in the United States: Predictors and implications for intervention development. Clinical Infectious Diseases, 56(2), 283–290. PMID: 23139252 [top]
- Tassiopoulos, K., Read, J. S., Brogly, S., Rich, K., Lester, B., Spector, S. A., . . . Seage, G. R., III. (2010). Substance use in HIV-Infected women during pregnancy: Self-report versus meconium analysis. AIDS and Behavior 14(6), 1269–1278. PMID: 20532607 [top]
- Griner R, Williams PL, Read JS, Seage GR 3rd, Crain M, Yogev R, Hazra R, Rich K. (2011). In utero and postnatal exposure to antiretrovirals among HIV-exposed but uninfected children in the United States. AIDS Patient Care and STDS, 25(7), 385–394. PMID: 21992592 [top]