Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Pediatric HIV infection: Classification, clinical manifestations, and outcome

Susan L Gillespie, MD, PhD
Section Editor
Mary E Paul, MD
Deputy Editor
Carrie Armsby, MD, MPH


Considerable progress has been made towards eliminating human immunodeficiency virus (HIV) among children; however, the global burden of pediatric HIV and acquired immune deficiency syndrome (AIDS) remains a challenge for healthcare workers around the world, particularly in resource-limited settings [1].

The case definition and classification of pediatric HIV infection, clinical manifestations of some of the AIDS-defining conditions (table 1), and outcomes of HIV infection in children are reviewed here. The epidemiology of pediatric HIV, prophylactic treatment of infants born to HIV-infected mothers, diagnostic testing for HIV in young children, the approach to febrile HIV-infected infants and children, and issues related to HIV infection in adolescents are discussed separately:

(See "Epidemiology of pediatric HIV infection".)

(See "Antiretroviral treatment of pregnant HIV-infected women and antiretroviral prophylaxis of their infants in resource-rich settings", section on 'Infant prophylaxis'.)

(See "Diagnostic testing for HIV infection in infants and children younger than 18 months".)


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Feb 25, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Luzuriaga K, Mofenson LM. Challenges in the Elimination of Pediatric HIV-1 Infection. N Engl J Med 2016; 374:761.
  2. Centers for Disease Control and Prevention (CDC). Revised surveillance case definition for HIV infection--United States, 2014. MMWR Recomm Rep 2014; 63:1.
  3. Schneider E, Whitmore S, Glynn KM, et al. Revised surveillance case definitions for HIV infection among adults, adolescents, and children aged <18 months and for HIV infection and AIDS among children aged 18 months to <13 years--United States, 2008. MMWR Recomm Rep 2008; 57:1.
  4. World Health Organization. WHO case definitions of HIV for surveillance and revised clinical staging and immunologic classification of HIV-related disease in adults and children. World Health Organization, Geneva, Switzerland, 2007, 1-48.
  5. World Health Organization. Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV. September 2015. (Available online at www.who.int/hiv/pub/guidelines/earlyrelease-arv/en/).
  6. Dankner WM, Lindsey JC, Levin MJ, Pediatric AIDS Clinical Trials Group Protocol Teams 051, 128, 138, 144, 152, 179, 190, 220, 240, 245, 254, 300 and 327. Correlates of opportunistic infections in children infected with the human immunodeficiency virus managed before highly active antiretroviral therapy. Pediatr Infect Dis J 2001; 20:40.
  7. Nesheim SR, Kapogiannis BG, Soe MM, et al. Trends in opportunistic infections in the pre- and post-highly active antiretroviral therapy eras among HIV-infected children in the Perinatal AIDS Collaborative Transmission Study, 1986-2004. Pediatrics 2007; 120:100.
  8. Candiani TM, Pinto J, Cardoso CA, et al. Impact of highly active antiretroviral therapy (HAART) on the incidence of opportunistic infections, hospitalizations and mortality among children and adolescents living with HIV/AIDS in Belo Horizonte, Minas Gerais State, Brazil. Cad Saude Publica 2007; 23 Suppl 3:S414.
  9. Kourtis AP, Bansil P, Posner SF, et al. Trends in hospitalizations of HIV-infected children and adolescents in the United States: analysis of data from the 1994-2003 Nationwide Inpatient Sample. Pediatrics 2007; 120:e236.
  10. Simonds RJ, Oxtoby MJ, Caldwell MB, et al. Pneumocystis carinii pneumonia among US children with perinatally acquired HIV infection. JAMA 1993; 270:470.
  11. Fatti GL, Zar HJ, Swingler GH. Clinical indicators of Pneumocystis jiroveci pneumonia (PCP) in South African children infected with the human immunodeficiency virus. Int J Infect Dis 2006; 10:282.
  12. Fujii T, Nakamura T, Iwamoto A. Pneumocystis pneumonia in patients with HIV infection: clinical manifestations, laboratory findings, and radiological features. J Infect Chemother 2007; 13:1.
  13. Surve TY, Rathod AD. Role of naso-gastric aspirate in HIV-positive children presenting with respiratory symptoms. J Trop Pediatr 2006; 52:451.
  14. Morrow BM, Samuel CM, Zampoli M, et al. Pneumocystis pneumonia in South African children diagnosed by molecular methods. BMC Res Notes 2014; 7:26.
  15. Samuel CM, Whitelaw A, Corcoran C, et al. Improved detection of Pneumocystis jirovecii in upper and lower respiratory tract specimens from children with suspected pneumocystis pneumonia using real-time PCR: a prospective study. BMC Infect Dis 2011; 11:329.
  16. Mofenson LM, Brady MT, Danner SP, et al. Guidelines for the Prevention and Treatment of Opportunistic Infections among HIV-exposed and HIV-infected children: recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics. MMWR Recomm Rep 2009; 58:1.
  17. American Academy of Pediatrics. Pneumocystis jirovecii infections. In: Red Book: 2015 Report of the Committee on Infectious Diseases, 30th, Kimberlin DW (Ed), American Academy of Pediatrics, Elk Grove Village, IL 2015. p.638.
  18. Katkin JP, Hansen TN, Langston C, et al. Pulmonary manifestations of AIDS in children. Semin Pediatr Infect Dis 1990; 1:40.
  19. Bernstein LJ, Krieger BZ, Novick B, et al. Bacterial infection in the acquired immunodeficiency syndrome of children. Pediatr Infect Dis 1985; 4:472.
  20. Krasinski K, Borkowsky W, Holzman RS. Prognosis of human immunodeficiency virus infection in children and adolescents. Pediatr Infect Dis J 1989; 8:216.
  21. Tovo PA, de Martino M, Gabiano C, et al. Prognostic factors and survival in children with perinatal HIV-1 infection. The Italian Register for HIV Infections in Children. Lancet 1992; 339:1249.
  22. Chiou CC, Groll AH, Gonzalez CE, et al. Esophageal candidiasis in pediatric acquired immunodeficiency syndrome: clinical manifestations and risk factors. Pediatr Infect Dis J 2000; 19:729.
  23. Tahan TT, Bruck I, Burger M, Cruz CR. Neurological profile and neurodevelopment of 88 children infected with HIV and 84 seroreverter children followed from 1995 to 2002. Braz J Infect Dis 2006; 10:322.
  24. Mintz M, Epstein LG, Koenigsberger MR. Neurological manifestations of acquired immunodeficiency syndrome in children. Int Pediatr 1989; 4:161.
  25. Michaels J, Sharer LR, Epstein LG. Human immunodeficiency virus type 1 (HIV-1) infection of the nervous system: a review. Immunodefic Rev 1988; 1:71.
  26. Sharer LR, Epstein LG, Cho ES, et al. Pathologic features of AIDS encephalopathy in children: evidence for LAV/HTLV-III infection of brain. Hum Pathol 1986; 17:271.
  27. Van Rie A, Mupuala A, Dow A. Impact of the HIV/AIDS epidemic on the neurodevelopment of preschool-aged children in Kinshasa, Democratic Republic of the Congo. Pediatrics 2008; 122:e123.
  28. Van Rie A, Dow A, Mupuala A, Stewart P. Neurodevelopmental trajectory of HIV-infected children accessing care in Kinshasa, Democratic Republic of Congo. J Acquir Immune Defic Syndr 2009; 52:636.
  29. Baillieu N, Potterton J. The extent of delay of language, motor, and cognitive development in HIV-positive infants. J Neurol Phys Ther 2008; 32:118.
  30. Nachman S, Chernoff M, Williams P, et al. Human immunodeficiency virus disease severity, psychiatric symptoms, and functional outcomes in perinatally infected youth. Arch Pediatr Adolesc Med 2012; 166:528.
  31. Lobato MN, Caldwell MB, Ng P, Oxtoby MJ. Encephalopathy in children with perinatally acquired human immunodeficiency virus infection. Pediatric Spectrum of Disease Clinical Consortium. J Pediatr 1995; 126:710.
  32. Cooper ER, Hanson C, Diaz C, et al. Encephalopathy and progression of human immunodeficiency virus disease in a cohort of children with perinatally acquired human immunodeficiency virus infection. Women and Infants Transmission Study Group. J Pediatr 1998; 132:808.
  33. Shanbhag MC, Rutstein RM, Zaoutis T, et al. Neurocognitive functioning in pediatric human immunodeficiency virus infection: effects of combined therapy. Arch Pediatr Adolesc Med 2005; 159:651.
  34. Lindsey JC, Malee KM, Brouwers P, et al. Neurodevelopmental functioning in HIV-infected infants and young children before and after the introduction of protease inhibitor-based highly active antiretroviral therapy. Pediatrics 2007; 119:e681.
  35. Smith R, Malee K, Leighty R, et al. Effects of perinatal HIV infection and associated risk factors on cognitive development among young children. Pediatrics 2006; 117:851.
  36. Patel K, Ming X, Williams PL, et al. Impact of HAART and CNS-penetrating antiretroviral regimens on HIV encephalopathy among perinatally infected children and adolescents. AIDS 2009; 23:1893.
  37. Paramesparan Y, Garvey LJ, Ashby J, et al. High rates of asymptomatic neurocognitive impairment in vertically acquired HIV-1-infected adolescents surviving to adulthood. J Acquir Immune Defic Syndr 2010; 55:134.
  38. Crowell CS, Malee KM, Yogev R, Muller WJ. Neurologic disease in HIV-infected children and the impact of combination antiretroviral therapy. Rev Med Virol 2014; 24:316.
  39. Puthanakit T, Aurpibul L, Louthrenoo O, et al. Poor cognitive functioning of school-aged children in thailand with perinatally acquired HIV infection taking antiretroviral therapy. AIDS Patient Care STDS 2010; 24:141.
  40. Puthanakit T, Saphonn V, Ananworanich J, et al. Early versus deferred antiretroviral therapy for children older than 1 year infected with HIV (PREDICT): a multicentre, randomised, open-label trial. Lancet Infect Dis 2012; 12:933.
  41. Puthanakit T, Ananworanich J, Vonthanak S, et al. Cognitive function and neurodevelopmental outcomes in HIV-infected Children older than 1 year of age randomized to early versus deferred antiretroviral therapy: the PREDICT neurodevelopmental study. Pediatr Infect Dis J 2013; 32:501.
  42. Laughton B, Cornell M, Grove D, et al. Early antiretroviral therapy improves neurodevelopmental outcomes in infants. AIDS 2012; 26:1685.
  43. Letendre SL, McCutchan JA, Childers ME, et al. Enhancing antiretroviral therapy for human immunodeficiency virus cognitive disorders. Ann Neurol 2004; 56:416.
  44. Eggers C, Hertogs K, Stürenburg HJ, et al. Delayed central nervous system virus suppression during highly active antiretroviral therapy is associated with HIV encephalopathy, but not with viral drug resistance or poor central nervous system drug penetration. AIDS 2003; 17:1897.
  45. Canestri A, Lescure FX, Jaureguiberry S, et al. Discordance between cerebral spinal fluid and plasma HIV replication in patients with neurological symptoms who are receiving suppressive antiretroviral therapy. Clin Infect Dis 2010; 50:773.
  46. Marra CM, Zhao Y, Clifford DB, et al. Impact of combination antiretroviral therapy on cerebrospinal fluid HIV RNA and neurocognitive performance. AIDS 2009; 23:1359.
  47. Tozzi V, Balestra P, Salvatori MF, et al. Changes in cognition during antiretroviral therapy: comparison of 2 different ranking systems to measure antiretroviral drug efficacy on HIV-associated neurocognitive disorders. J Acquir Immune Defic Syndr 2009; 52:56.
  48. Ellington SR, Clarke KE, Kourtis AP. Cytomegalovirus Infection in Human Immunodeficiency Virus (HIV)-Exposed and HIV-Infected Infants: A Systematic Review. J Infect Dis 2016; 213:891.
  49. Moses A, Nelson J, Bagby GC Jr. The influence of human immunodeficiency virus-1 on hematopoiesis. Blood 1998; 91:1479.
  50. Lipshultz SE, Easley KA, Orav EJ, et al. Cardiovascular status of infants and children of women infected with HIV-1 (P(2)C(2) HIV): a cohort study. Lancet 2002; 360:368.
  51. Al-Attar I, Orav EJ, Exil V, et al. Predictors of cardiac morbidity and related mortality in children with acquired immunodeficiency syndrome. J Am Coll Cardiol 2003; 41:1598.
  52. Spira R, Lepage P, Msellati P, et al. Natural history of human immunodeficiency virus type 1 infection in children: a five-year prospective study in Rwanda. Mother-to-Child HIV-1 Transmission Study Group. Pediatrics 1999; 104:e56.
  53. Newell ML, Coovadia H, Cortina-Borja M, et al. Mortality of infected and uninfected infants born to HIV-infected mothers in Africa: a pooled analysis. Lancet 2004; 364:1236.
  54. Gray L, Newell ML, Thorne C, et al. Fluctuations in symptoms in human immunodeficiency virus-infected children: the first 10 years of life. Pediatrics 2001; 108:116.
  55. Blanche S, Newell ML, Mayaux MJ, et al. Morbidity and mortality in European children vertically infected by HIV-1. The French Pediatric HIV Infection Study Group and European Collaborative Study. J Acquir Immune Defic Syndr Hum Retrovirol 1997; 14:442.
  56. Mbori-Ngacha D, Nduati R, John G, et al. Morbidity and mortality in breastfed and formula-fed infants of HIV-1-infected women: A randomized clinical trial. JAMA 2001; 286:2413.
  57. Mphatswe W, Blanckenberg N, Tudor-Williams G, et al. High frequency of rapid immunological progression in African infants infected in the era of perinatal HIV prophylaxis. AIDS 2007; 21:1253.
  58. Penazzato M, Prendergast AJ, Muhe LM, et al. Optimisation of antiretroviral therapy in HIV-infected children under 3 years of age. Cochrane Database Syst Rev 2014; :CD004772.
  59. Chiappini E, Galli L, Tovo PA, et al. Five-year follow-up of children with perinatal HIV-1 infection receiving early highly active antiretroviral therapy. BMC Infect Dis 2009; 9:140.
  60. Guillén S, García San Miguel L, Resino S, et al. Opportunistic infections and organ-specific diseases in HIV-1-infected children: a cohort study (1990-2006). HIV Med 2010; 11:245.
  61. Le Doaré K, Bland R, Newell ML. Neurodevelopment in children born to HIV-infected mothers by infection and treatment status. Pediatrics 2012; 130:e1326.
  62. de Martino M, Tovo PA, Balducci M, et al. Reduction in mortality with availability of antiretroviral therapy for children with perinatal HIV-1 infection. Italian Register for HIV Infection in Children and the Italian National AIDS Registry. JAMA 2000; 284:190.
  63. Gortmaker SL, Hughes M, Cervia J, et al. Effect of combination therapy including protease inhibitors on mortality among children and adolescents infected with HIV-1. N Engl J Med 2001; 345:1522.
  64. Gona P, Van Dyke RB, Williams PL, et al. Incidence of opportunistic and other infections in HIV-infected children in the HAART era. JAMA 2006; 296:292.
  65. Sauvageot D, Schaefer M, Olson D, et al. Antiretroviral therapy outcomes in resource-limited settings for HIV-infected children <5 years of age. Pediatrics 2010; 125:e1039.
  66. Peacock-Villada E, Richardson BA, John-Stewart GC. Post-HAART outcomes in pediatric populations: comparison of resource-limited and developed countries. Pediatrics 2011; 127:e423.
  67. Brady MT, Oleske JM, Williams PL, et al. Declines in mortality rates and changes in causes of death in HIV-1-infected children during the HAART era. J Acquir Immune Defic Syndr 2010; 53:86.
  68. Berti E, Thorne C, Noguera-Julian A, et al. The new face of the pediatric HIV epidemic in Western countries: demographic characteristics, morbidity and mortality of the pediatric HIV-infected population. Pediatr Infect Dis J 2015; 34:S7.
  69. Chiappini E, Galli L, Tovo PA, et al. Changing patterns of clinical events in perinatally HIV-1-infected children during the era of HAART. AIDS 2007; 21:1607.
  70. Judd A, Doerholt K, Tookey PA, et al. Morbidity, mortality, and response to treatment by children in the United Kingdom and Ireland with perinatally acquired HIV infection during 1996-2006: planning for teenage and adult care. Clin Infect Dis 2007; 45:918.
  71. Palladino C, Climent FJ, José MI, et al. Causes of death in pediatric patients vertically infected by the human immunodeficiency virus type 1 in Madrid, Spain, from 1982 to mid-2009. Pediatr Infect Dis J 2011; 30:495.
  72. Kapogiannis BG, Soe MM, Nesheim SR, et al. Mortality trends in the US Perinatal AIDS Collaborative Transmission Study (1986-2004). Clin Infect Dis 2011; 53:1024.
  73. Mirani G, Williams PL, Chernoff M, et al. Changing Trends in Complications and Mortality Rates Among US Youth and Young Adults With HIV Infection in the Era of Combination Antiretroviral Therapy. Clin Infect Dis 2015; 61:1850.
  74. Fenner L, Brinkhof MW, Keiser O, et al. Early mortality and loss to follow-up in HIV-infected children starting antiretroviral therapy in Southern Africa. J Acquir Immune Defic Syndr 2010; 54:524.
  75. KIDS-ART-LINC Collaboration. Low risk of death, but substantial program attrition, in pediatric HIV treatment cohorts in Sub-Saharan Africa. J Acquir Immune Defic Syndr 2008; 49:523.
  76. Davies MA, Keiser O, Technau K, et al. Outcomes of the South African National Antiretroviral Treatment Programme for children: the IeDEA Southern Africa collaboration. S Afr Med J 2009; 99:730.
  77. Ciaranello AL, Chang Y, Margulis AV, et al. Effectiveness of pediatric antiretroviral therapy in resource-limited settings: a systematic review and meta-analysis. Clin Infect Dis 2009; 49:1915.
  78. Bolton-Moore C, Mubiana-Mbewe M, Cantrell RA, et al. Clinical outcomes and CD4 cell response in children receiving antiretroviral therapy at primary health care facilities in Zambia. JAMA 2007; 298:1888.
  79. Walker AS, Prendergast AJ, Mugyenyi P, et al. Mortality in the year following antiretroviral therapy initiation in HIV-infected adults and children in Uganda and Zimbabwe. Clin Infect Dis 2012; 55:1707.
  80. Davies MA, May M, Bolton-Moore C, et al. Prognosis of children with HIV-1 infection starting antiretroviral therapy in Southern Africa: a collaborative analysis of treatment programs. Pediatr Infect Dis J 2014; 33:608.
  81. Violari A, Cotton MF, Gibb DM, et al. Early antiretroviral therapy and mortality among HIV-infected infants. N Engl J Med 2008; 359:2233.
  82. World Health Organization. Antiretroviral therapy of HIV infection in infants and children: towards universal access: Recommendation for a public health approach. World Health Organization, Geneva, Switzerland, 2010, 1- 206.
  83. Koller M, Patel K, Chi BH, et al. Immunodeficiency in children starting antiretroviral therapy in low-, middle-, and high-income countries. J Acquir Immune Defic Syndr 2015; 68:62.
  84. Fortuny C, Deyà-Martínez Á, Chiappini E, et al. Metabolic and renal adverse effects of antiretroviral therapy in HIV-infected children and adolescents. Pediatr Infect Dis J 2015; 34:S36.
  85. Shahinian V, Rajaraman S, Borucki M, et al. Prevalence of HIV-associated nephropathy in autopsies of HIV-infected patients. Am J Kidney Dis 2000; 35:884.
  86. Papi L, Menezes AC, Rocha H, et al. Prevalence of lipodystrophy and risk factors for dyslipidemia in HIV-infected children in Brazil. Braz J Infect Dis 2014; 18:394.
  87. Miller TI, Borkowsky W, DiMeglio LA, et al. Metabolic abnormalities and viral replication are associated with biomarkers of vascular dysfunction in HIV-infected children. HIV Med 2012; 13:264.
  88. Lipshultz SE, Williams PL, Wilkinson JD, et al. 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 Pediatr 2013; 167:520.
  89. Lipshultz SE, Miller TL, Wilkinson JD, et al. Cardiac effects in perinatally HIV-infected and HIV-exposed but uninfected children and adolescents: a view from the United States of America. J Int AIDS Soc 2013; 16:18597.
  90. DiMeglio LA, Wang J, Siberry GK, et al. Bone mineral density in children and adolescents with perinatal HIV infection. AIDS 2013; 27:211.
  91. Chernoff M, Nachman S, Williams P, et al. Mental health treatment patterns in perinatally HIV-infected youth and controls. Pediatrics 2009; 124:627.
  92. Gadow KD, Angelidou K, Chernoff M, et al. Longitudinal study of emerging mental health concerns in youth perinatally infected with HIV and peer comparisons. J Dev Behav Pediatr 2012; 33:456.
  93. Mellins CA, Elkington KS, Leu CS, et al. Prevalence and change in psychiatric disorders among perinatally HIV-infected and HIV-exposed youth. AIDS Care 2012; 24:953.