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Children and Adolescents With Perinatal HIV Infection or Exposure

September 12, 2023

Commentary From the Committee on Pediatric and Adolescent HIV

The first cases of AIDS in children were reported by the Centers of Disease Control and Prevention approximately 18 months after the first AIDS reports in adults. In New York, New Jersey, and California, infection in infants was associated with unexplained immunodeficiency and opportunistic infections.1,2 By 1983, reports of AIDS with high mortality were noted among young children from New York City, Newark, and Miami who were born to parents with recognized risk factors.3-5 The American Academy of Pediatrics (AAP) has been at the forefront of research in pediatric HIV infection since the beginning of the epidemic. The first set of guidelines pertaining to management of children and adolescents with HIV in school, day care and foster care settings were published by the AAP Committee on Infectious Diseases in 1986-1987, only 4 years after HIV in children was first recognized in 1982. In response to rapidly increasing numbers of children with HIV infection in the United States, the AAP developed a Task Force on Pediatric AIDS in 1987, which became the Provisional Committee on Pediatric AIDS in 1992, the Committee on Pediatric AIDS in 1995, and is currently the Committee on Pediatric and Adolescent HIV (COPAH). The mission of these committees has been to develop and disseminate evidence-based guidelines and recommendations on the management of infants, children, adolescents, and young adults at risk for and living with HIV in the form of state-of-the-art clinical reports, technical reports, and policy statements. Over the past 4 decades, Pediatrics has given voice to more than 40 critically important publications from these committees. We highlight just some of these key articles below.

Children and Adolescents With Perinatal HIV Infection or Exposure

Natella Rakhmanina, MD, FAAP,1,2,3 Rana Chakraborty, MD, FAAP2,4,5 Lynne Mofenson, MD, FAAP1

Affiliations: 1Divison of Infectious Diseases, Children’s National Hospital, Washington, DC; 2Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC; 3Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC; 4Department of Obstetrics and Gynecology, Mayo Clinic College of Medicine, Rochester, MN; 5Department of Pediatric and Adolescent Medicine, Division of Infectious Diseases, Mayo Clinic College of Medicine, Rochester, MN; 6Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN

Highlighted Articles From Pediatrics

The Early Years of the Pediatric HIV Epidemic

Dr. Martha Rogers published the first summary of US national pediatric AIDS surveillance data in Pediatrics, noting the case numbers reported in 1985 more than doubled from those in 1984. Dr. Rogers noted that children most commonly acquired HIV from their infected mothers by perinatal transmission.6 These findings presaged the continued rapid increase in cases prior to the pivotal 1994 PACTG 076 clinical trial, which showed that maternal antenatal and intrapartum treatment followed by 6 weeks of infant treatment with zidovudine (ZDV) could prevent perinatal transmission.

Although the global nature of HIV in children went relatively unrecognized in the early years of the epidemic, it was Pediatrics that published one of the first papers by Dr. Jonathan Mann describing an 11% HIV seroprevalence among hospitalized children in Zaire (now the Democratic Republic of Congo) and higher hospitalization rates and in-hospital mortality compared to seronegative children.7 Foretelling events, Dr. Mann commented that “in areas of the world where women of childbearing age may be at increased risk of HIV infection, pediatric HIV infections may become correspondingly important.”

By the early 1990s, HIV/AIDS was recognized as an increasing cause of childhood mortality in the United States. Dr. Chu and colleagues noted that in New York State by 1988, HIV/AIDS was the leading cause of death in Hispanic and second leading cause of death in Black children aged 1-4 years; nationally, HIV was the ninth leading cause of death among all children aged 1-4 years and sixth leading cause of death among Black children in this age group.8 She noted that in the setting of an estimated annual rate of 1,500-2,000 neonates infected with HIV at birth, that the effect of HIV on mortality in children would only increase.

The Beginning of the Pediatric Treatment Era in the United States

Given the increasing rates of HIV-associated morbidity and mortality among children in the United States and across the world, significant efforts were dedicated to understanding the pathogenesis of HIV infection and to the development of therapeutic interventions. The recognition that viral burden was associated with symptomatic HIV disease in children and that ZDV, approved for treatment of HIV in children in 1991, significantly, albeit temporarily, reduced viral titer was published in Pediatrics by Dr. Srugo and colleagues.9 This study provided an important foundation for future pediatric HIV trials and therapeutics. While ZDV treatment in children led to moderate improvements in morbidity and mortality, with the approval of other antiretroviral (ARV) agents, new approaches using combination antiretroviral therapy (ART) began to be investigated. In 1994, Dr. Husson and colleagues reported in Pediatrics on treatment with ZDV combined with didanosine in treatment-naïve children, and observed potent immunologic improvement and antiviral activity without new or enhanced toxicity.10 This study was among the first to note that “combination therapy with nucleoside analogues may be important in the treatment of HIV infection” and augured the development of more potent triple ART in the next 2 decades using nucleoside transcriptase and protease inhibitors.

Expansion of Pediatric HIV Treatment to Resource-Limited Settings

With the development of more potent ART regimens, in the United States a welcome decline in pediatric HIV/AIDS mortality was observed, but access to ART for children in resource-limited countries remained constrained. Several papers in Pediatrics demonstrated the feasibility of ART provision to children in sub-Saharan Africa and the importance of early HIV diagnosis and treatment. Dr. Sauvageot and colleagues described the experience of Doctors Without Borders with respect to providing ART to nearly 4,000 children under age 5 years on 2 continents (Africa and Asia). The study demonstrated that ART delivery to children with HIV was achievable in resource-limited settings and achieved encouraging clinical outcomes. Survival rates were lowest in the youngest children (<12 months), emphasizing the need for early HIV diagnosis and treatment.11 A report from the Baylor International Pediatric AIDS Initiative by Dr. Kabue and colleagues described their experience with pediatric treatment in over 2,300 children with HIV in Malawi, Lesotho, and Swaziland in which they reported low mortality rates and good treatment outcomes.12 This report also highlighted significant gaps in retention and viral suppression among infants <12 months of age and called for development of more suitable treatment options/formulations in young infants.

Long-Term Effects of HIV Infection and Treatment and HIV-Exposure in Children and Adolescents

As survival of children and adolescents living with HIV began to increase, attention expanded to the effects of HIV and ART drugs on long-term health, including outcomes among those uninfected children with perinatal HIV exposure. The European Collaborative Study reported on clinical and immune outcomes among perinatally infected children followed prospectively in 11 European centers through age 10 years, reporting that children born after 1994, when earlier ART initiation was introduced, were significantly less likely to have disease progression than those born when treatment was not widely available or if had been limited to single drug therapy. Most children were asymptomatic, and fluctuations in clinical signs and symptoms were mainly associated with intermittent infections.13 In 2018, Dr. Abrams and colleagues published a study in Pediatrics on young adults in the United States who were on long-term ART for perinatally acquired HIV or who had been perinatally exposed but uninfected. They found that young adults with HIV did achieve adulthood milestones related to school, employment, sexual relationships, and starting families. Noting high rates of psychiatric morbidity, substance use disorders, and behavioral risks among both HIV-infected and HIV-exposed young adults, they called for attention “to the growing population of perinatally HIV-exposed but uninfected young adults.”14

Adolescents and Risk for HIV Infection

Globally, adolescents and young adults face not only a burden of perinatal HIV infection, but also high rates of horizontally acquired HIV. A publication in Pediatrics from 1993 from Dr. Futterman and colleagues in New York was among the first to recognize that HIV had entered the adolescent population as a common sexually transmitted infection and noted the critical need to develop risk-reduction strategies targeted to vulnerable and affected populations.15 Reflecting nationwide efforts to identify and prevent HIV in adolescents, the 2003 study published in Pediatrics by Dr. Murphy and colleagues advocated for routine normalized widescale HIV testing in the United States.16 A recent 2020 study published in Pediatrics by Dr. Mustanski and colleagues that highlighted low rates of HIV testing among adolescent men who had sex with men in the US underscores the critical need for US pediatricians to “be integral to achieving testing rates needed to end the epidemic.”17


While writing this commentary, we have reviewed several hundred excellent HIV-related publications in Pediatrics over the last 40 years of the pandemic, of which we highlighted only a few. The AAP and Pediatrics have been and will remain leaders, critical partners, and strong advocates in the efforts to achieve national and global pediatric and adolescent HIV targets.


  1. Centers for Disease Control and Prevention. Unexplained immunodeficiency and opportunistic infections in infants--New York, New Jersey, California. MMWR Morb Mortal Wkly Rep. 1982;31(49):665-667
  2. Centers for Disease Control and Prevention. Pneumocystis pneumonia—Los Angeles, 1981. JAMA. 1996;276(13):1020-1022
  3. Oleske J, Minnefor A, Cooper R Jr, et al. Immune deficiency syndrome in children. JAMA. 1983;249(17):2345-2349
  4. Rubinstein A, Sicklick M, Gupta A, et al. Acquired immunodeficiency with reversed T4/T8 ratios in infants born to promiscuous and drug-addicted mothers. JAMA. 1983;249(17):2350-2356
  5. Scott GB, Buck BE, Leterman JG, Bloom FL, Parks WP. Acquired immunodeficiency syndrome in infants. N Engl J Med. 1984;310(2):76-81
  6. Rogers MF, Thomas PA, Starcher ET, Noa MC, Bush TJ, Jaffe HW. Acquired immunodeficiency syndrome in children: report of the Centers for Disease Control National Surveillance, 1982 to 1985. Pediatrics. 1987;79(6):1008-1014
  7. Mann JM, Francis H, Davachi F, et al. Human immunodeficiency virus seroprevalence in pediatric patients 2 to 14 years of age at Mama Yemo Hospital, Kinshasa, Zaire. Pediatrics. 1986;78(4):673-677
  8. Chu SY, Buehler JW, Oxtoby MJ, Kilbourne BW. Impact of the human immunodeficiency virus epidemic on mortality in children, United States. Pediatrics. 1991;87(6):806-810
  9. Srugo I, Brunell PA, Chelyapov NV, Ho DD, Alam M, Israele V. Virus burden in human immunodeficiency virus type 1-infected children: relationship to disease status and effect of antiviral therapy. Pediatrics. 1991;87(6):921-925
  10. Husson RN, Mueller BU, Farley M et al. Zidovudine and didanosine combination therapy in children with human immunodeficiency virus infection. 1994;93(2):316-322
  11. Sauvageot D, Schaefer M, Olson D, Pujades-Rodriguez M, O’Brien DP. Antiretroviral therapy outcomes in resource-limited settings for HIV-infected children <5 years of age. Pediatrics. 2010;125(5):e1039-e1047
  12. Kabue MM, Buck WC, Wanless SR, et al. Mortality and clinical outcomes in HIV-infected children on antiretroviral therapy in Malawi, Lesotho, and Swaziland. Pediatrics. 2012;130(3):e591-e599
  13. Gray L, Newell ML, Thorne C, Peckham C, Levy J, European Collaborative Study. Fluctuations in symptoms in human immunodeficiency virus-infected children: the first 10 years of life. Pediatrics. 2001;108(1):116-122
  14. Abrams EJ, Mellins CA, Bucek A, et al. Behavioral health and adult milestones in young adults with perinatal HIV infection or exposure. Pediatrics. 2018;142(3):e20180938
  15. Futterman D, Hein K, Reuben N, Dell R, Shaffer N. Human immunodeficiency virus-infected adolescents: the first 50 patients in a New York City program. Pediatrics. 1993;91(4):730-735
  16. Murphy DA, Mitchell R, Vermund SH, Futterman D, Adolescent Medicine HIV/AIDS Research Network. Factors associated with HIV testing among HIV-positive and HIV-negative high-risk adolescents: the REACH Study. Pediatrics. 2002;110(3):e36-e41
  17. Mustanski B, Moskowitz DA, Moran KO, Rendina HJ, Newcomb ME, Macapagal K. Factors associated with HIV testing in teenage men who have sex with men. Pediatrics. 2020;145(3):e20192322
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