Pediatric Drugs

, Volume 6, Issue 6, pp 347–362

Management of Gastrointestinal Disorders in Children with HIV Infection

  • Alfredo Guarino
  • Eugenia Bruzzese
  • Giulio De Marco
  • Vittoria Buccigrossi
Therapy In Practice


A double scenario characterizes the epidemiology of HIV infection in children. In countries where highly active antiretroviral therapy (HAART) is available, the pattern of HIV infection is evolving into that of a chronic disease, for which control strictly depends on patients’ adherence to treatment. In developing countries with no or limited access to HAART, AIDS is rapidly expanding and is loaded with a high fatality ratio, due to the combined effects of malnutrition and opportunistic infections.

The digestive tract is a target of the disease in both settings. Opportunistic infections play a major role in children with severe immune impairment, with Cryptosporidium parvum being the leading agent of severe diarrhea. Several therapeutic approaches are effective in reducing fecal output, but the eradication of the parasite is rarely obtained. Other opportunistic infections may induce severe and protracted diarrhea, including atypical mycobacteria and cytomegalovirus. Diagnosis of diarrhea should be individually tailored based on presenting symptoms and risk factors. A stepwise approach is effective in limiting patient discomfort and minimizing the costs of investigations, starting with microbiologic investigation and proceeding with endoscopy and histology. Aggressive treatment of infectious diarrhea is required in severely immunocompromised children. However, antiretroviral therapy prevents the development of severe cryptosporidiosis.

The liver and pancreas are also target organs in HIV infection, although functional failure is rare. The digestive-absorptive functions are impaired, with steatorrhea, nutrient malabsorption, and increased permeability occurring in 20–70% of children. Intestinal dysfunction contributes to growth failure and further immune derangement, leading to wasting, the terminal stage of AIDS. Nutritional management is crucial in HIV-infected children and is based on aggressive nutritional rehabilitation through enteral or parenteral routes and micronutrient supplementation.

HIV may play a direct enteropathogenic role and is implicated in both diarrhea and intestinal dysfunction. This explains the efficacy of antiretroviral therapy in inducing remission of diarrhea and restoring intestinal function.

Gastrointestinal side effects of antiretroviral drugs are increasingly observed; they are often mild and transient. Severe reactions are rare but require the withdrawal of drugs.

In conclusion, severe enteric infections and intestinal dysfunction characterize the intestinal involvement of HIV infection. This is more common in, but not limited to, children who do not receive effective antiretroviral therapy. Diagnostic approaches include microbiologic and morphologic examinations and assessment of digestive processes, but immunologic and virologic data should be also carefully considered. Treatment is based upon specific anti-infectious drugs, antiretroviral therapy, and nutritional rehabilitation.


  1. 1.
    Mofenson LM. Pediatric HIV infection in developed and developing countries: epidemiology and natural history. In: Shearer WT, Hanson IC, editors. Medical management of AIDS in children. Philadelphia (PA): Saunders, 2003: 1–28Google Scholar
  2. 2.
    Selik RM, Lindegren ML. Changes in deaths reported with human immunodeficiency virus infection among United States children less than thirteen years old, 1987 through 1999. Pediatr Infect Dis J 2003; 22: 635–41PubMedGoogle Scholar
  3. 3.
    Gibb DM, Duong T, Tookey PA, et al. Decline in mortality, AIDS, and hospital admissions in perinatally HIV-1 infected children in the United Kingdom and Ireland. BMJ 2003; 327(7422): 1019PubMedCrossRefGoogle Scholar
  4. 4.
    Lindegren ML, Steinberg S, Byers Jr RH. Epidemiology of HIV/AIDS in children. Pediatr Clin North Am 2000; 47: 1–20PubMedCrossRefGoogle Scholar
  5. 5.
    Centers for Disease Control and Prevention. 1994 revised classification system for human immunodeficiency virus infection in children less than 13 years of age. MMWR Morb Mortal Wkly Rep 1994; 43: 1–10Google Scholar
  6. 6.
    Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for the use of antiretroviral agents in pediatric HIV infection [online]. Available from URL: [Accessed 2004 Jan 23]
  7. 7.
    Chantry CJ, Moye Jr J, Winter HS. Nutritional monitoring and support. In: Zeichner SL, Read JS, editors. Handbook of pediatric HIV care. Philadelphia (PA): Lippincott Williams & Wilkins, 1999: 188–209Google Scholar
  8. 8.
    Obimbo EM, Mbori-Ngacha DA, Ochieng JO, et al. Predictors of early mortality in a cohort of human immunodeficiency virus type 1-infected African children. Pediatr Infect Dis J 2004; 23: 536–43PubMedCrossRefGoogle Scholar
  9. 9.
    Guarino A, Castaldo A, Russo S, et al. Enteric cryptosporidiosis in pediatric HIV-infection. J Pediatr Gastroenterol Nutr 1997; 25: 182–7PubMedCrossRefGoogle Scholar
  10. 10.
    Monkemuller KE, Call SA, Lazenby AJ, et al. Declining prevalence of opportunistic gastrointestinal disease in the era of combination antiretroviral therapy. Am J Gastroenterol 2002; 95: 457–62Google Scholar
  11. 11.
    Guarino A, Albano F. Guidelines for the approach to outpatient children with acute diarrhoea. Acta Paediatr 2001; 90: 1087–95PubMedCrossRefGoogle Scholar
  12. 12.
    Keusch GT, Thea DM, Kamenga M, et al. Persistent diarrhea associated with AIDS. Acta Paediatr Suppl 1992; 381: 45–8PubMedCrossRefGoogle Scholar
  13. 13.
    Call SA, Heudebert G, Saag M, et al. The changing etiology of chronic diarrhea in HIV-infected patients with CD4 cell counts less than 200 cells/mm3. Am J Gastroenterol 2002; 95: 3142–6CrossRefGoogle Scholar
  14. 14.
    Chen XM, Keithly JS, Paya CV, et al. Cryptosporidiosis. N Engl J Med 2002; 346: 1723–31PubMedCrossRefGoogle Scholar
  15. 15.
    Koch J, Owen RL. Small intestine pathogens in AIDS: conventional and opportunistic. Gastrointest Endosc Clin N Am 1998; 8: 869–88PubMedGoogle Scholar
  16. 16.
    Goodgame RW, Kimball K, Ou CN, et al. Intestinal function and injury in acquired immunodeficiency syndrome-related cryptosporidiosis. Gastroenterology 1995; 108: 1075–82PubMedCrossRefGoogle Scholar
  17. 17.
    Kosek M, Alcantara C, Lima AA, et al. Cryptosporidiosis: an update. Lancet Infect Dis 2001; I: 262–9CrossRefGoogle Scholar
  18. 18.
    Guarino A, Berni Canani R, Casola A, et al. Human intestinal cryptosporidiosis: secretory diarrhea and enterotoxic activity in Caco-2 cells. J Infect Dis 1995; 171: 976–83PubMedCrossRefGoogle Scholar
  19. 19.
    Obi CL, Bessong PO. Diarrhoeagenic bacterial pathogens in HIV-positive patients in rural communities of Limpopo province, South Africa. J Health Popul Nutr 2002; 20: 230–4PubMedGoogle Scholar
  20. 20.
    Welage LS, Carver PL, Reyankar S, et al. Alterations in gastric acidity in patients infected with human immunodeficiency virus. Clin Infect Dis 1995; 21: 1431–8PubMedCrossRefGoogle Scholar
  21. 21.
    Parashar UD, Hummelmann E, Brese JS, et al. Global illness and deaths caused by rotavirus disease in children. Emerg Infect Dis 2003; 9: 565–72PubMedCrossRefGoogle Scholar
  22. 22.
    Cunliffe NA, Gondwe JS, Kirkwood CD, et al. Effect of concomitant HIV infection on presentation and outcome of gastroenteritis in Malawian children. Lancet 2001; 358: 550–5PubMedCrossRefGoogle Scholar
  23. 23.
    Guarino A, Russo S, Castaldo A, et al. Passive immunotherapy for rotavirus-induced diarrhoea in children with HIV infection. AIDS 1996; 10: 1176–8PubMedGoogle Scholar
  24. 24.
    Ukarapol N, Chartapisak W, Lertprasertsuk N, et al. Cytomegalovirus-associated manifestations involving the digestive tract in children with human immunodeficiency virus infection. J Pediatr Gastroenterol Nutr 2002; 35: 669–73PubMedCrossRefGoogle Scholar
  25. 25.
    Keusch GT, Thea DM, Kamenga M, et al. Persistent diarrhea associated with AIDS. Acta Paediatr 1992; 381: 45–8CrossRefGoogle Scholar
  26. 26.
    Jirapinyo P, Brewster D, Succi RC, et al. HIV disease: Working Group Report of the First World Congress of Pedatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr 2002; 35Suppl. 2: S134–42PubMedCrossRefGoogle Scholar
  27. 27.
    Cohen J, West AB, Bini EJ. Infectious diarrhea in human immunodeficiency virus. Gastroenterol Clin North Am 2001; 30: 637–64PubMedCrossRefGoogle Scholar
  28. 28.
    Ramos-Soriano AG, Saavedra JM, Wu TC, et al. Enteric pathogens associated with gastrointestinal dysfunction in children with HIV infection. Mol Cell Probes 1996; 10: 67–73PubMedCrossRefGoogle Scholar
  29. 29.
    Berni Canani R, Cirillo P, Mallardo G, et al. Effects of HIV-1 TAT protein on ion secretion and on cell proliferation in human intestinal epithelial cells. Gastroenterology 2003; 124: 368–76CrossRefGoogle Scholar
  30. 30.
    Wilcox CM, Rabeneck L, Friedman S. AGA technical review: malnutrition and cachexia, chronic diarrhea and hepatobiliary disease in patients with human immunodeficiency virus infection. Gastroenterology 1996; 111: 1724–36PubMedCrossRefGoogle Scholar
  31. 31.
    The Italian Paediatric Intestinal/HIV Study Group. Intestinal malabsorption of HIV-infected children: relationship to diarrhoea, failure to thrive, enteric microorganisms and immune impairment. AIDS 1993; 7: 1435–40CrossRefGoogle Scholar
  32. 32.
    Guarino A, Albano F. Viral diarrhea. In: Guandalini S, editor. Textbook of pediatric gastroenterology. London: Martin Dunitz Ltd, 2004: 127–44Google Scholar
  33. 33.
    Ball SC. Diarrhea in a patient with AIDS. AIDS Read 2002; 12: 380–8PubMedGoogle Scholar
  34. 34.
    Miller TL, McQuinn LB, Orav EJ. Endoscopy of the upper gastrointestinal tract as a diagnostic tool for children with human immunodeficiency virus infection. J Pediatr 1997; 130: 767–73Google Scholar
  35. 35.
    Arico M, Caselli D, D’Argenio P, et al. Malignancies in children with human immunodeficiency virus type 1 infection: the Italian Multicenter Study on Human Immunodeficiency Virus Infection in Children. Cancer 1991; 68: 2473–7PubMedCrossRefGoogle Scholar
  36. 36.
    Guarino A, Tarallo L, Guandalini S, et al. Impaired intestinal function in symptomatic HIV infection. J Pediatr Gastroenterol Nutr 1991; 12: 452–8CrossRefGoogle Scholar
  37. 37.
    Zulu I, Veitch A, Sianongo S, et al. Albendazole chemotherapy for AIDS-related diarrhoea in Zambia: clinical, parasitological and mucosal responses. Aliment Pharmacol Ther 2002; 16: 595–601PubMedCrossRefGoogle Scholar
  38. 38.
    Amadi B, Mwiya M, Musuku J, et al. Effect of nitazoxamide on morbidity and mortality in Zambian children with cryptosporidiosis: a randomized controlled trial. Lancet 2002; 360: 1375–80PubMedCrossRefGoogle Scholar
  39. 39.
    Greenberg PD, Cello JP. Treatment of severe diarrhea caused by Cryptosporidium parvum with oral bovine immunoglobulin concentrate in patients with AIDS. J Acquir Immune Defic Syndr Hum Retrovirol 1996; 13: 348–54PubMedCrossRefGoogle Scholar
  40. 40.
    Guarino A, Berni Canani R, Spagnuolo MI, et al. In vivo and in vitro efficacy of octreotide for treatment of enteric cryptosporidiosis. Dig Dis Sci 1998; 43: 436–41PubMedCrossRefGoogle Scholar
  41. 41.
    Gibb DM, Newberry A, Klein N, et al. Immune repopulation after HAART in previously treated HIV-1-infected children: Paediatric European Network for Treatment of AIDS (PENTA) Steering Committee. Lancet 2000; 355: 1331–2PubMedCrossRefGoogle Scholar
  42. 42.
    Guarino A, Albano F, Berni Canani R, et al. HIV, fatal rotavirus infection, and treatment options. Lancet 2002; 359: 74PubMedCrossRefGoogle Scholar
  43. 43.
    Simonsen L, Morens DM, Elixhauser A, et al. Effect of rotavirus vaccination programme on trends in admission of infants to hospital for intussusception. Lancet 2001; 358: 1224–9PubMedCrossRefGoogle Scholar
  44. 44.
    Kimberlin DW. Antiviral therapy for cytomegalovirus infections in pediatric patients. Semin Pediatr Infect Dis 2002; 13: 22–30PubMedCrossRefGoogle Scholar
  45. 45.
    Shafran S, Singer J, Zarowny D, et al. A comparison of two regimens for the treatment of Mycobacterium avium complex bacteremia in AIDS: rifabutin, ethambutol, and clarithromycin versus rifampin, ethambutol, clofazimine, and ciprofloxacin. N Engl J Med 1996; 335: 377–83PubMedCrossRefGoogle Scholar
  46. 46.
    Neild PJ, Evans DF, Castillo FD, et al. Effect of octreotide on small intestinal motility in HIV-infected patients with chronic refractory diarrhea. Dig Dis Sci 2001; 46: 2636–42PubMedCrossRefGoogle Scholar
  47. 47.
    Minton NA, Henry JA. Loperamide poisoning in children. Lancet 1990; 335: 788PubMedCrossRefGoogle Scholar
  48. 48.
    Tovo PA, de Martino M, Gabiano C, et al. Prognostic factors and survival in children with perinatal HIV-1 infection. Lancet 1992; 339: 1249–53PubMedCrossRefGoogle Scholar
  49. 49.
    Castaldo A, Tarallo L, Palomba E, et al. Iron deficiency and intestinal malabsorption in HIV disease. J Pediatr Gastroenterol Nutr 1996; 22: 359–63PubMedCrossRefGoogle Scholar
  50. 50.
    Zuin G, Fontana M, Monti S, et al. Malabsorption of different lactose loads in children with human immunodeficiency virus infection. J Pediatr Gastroenterol Nutr 1992; 15: 408–12PubMedCrossRefGoogle Scholar
  51. 51.
    Carroccio A, Fontana M, Spagnuolo MI, et al. Pancreatic dysfunction and its association with fat malabsorption in HIV infected children. Gut 1998; 43: 558–63PubMedCrossRefGoogle Scholar
  52. 52.
    Berni Canani R, Spagnuolo MI, Cirillo P, et al. Ritonavir combination therapy restores intestinal function in children with advanced HIV disease. J Acquir Immune Defic Syndr 1999; 21: 307–12CrossRefGoogle Scholar
  53. 53.
    Ferrero S, Lungaro P, Bruzzone BM, et al. Prospective study of mother-to-infant transmission of hepatitis C virus: a 10-year survey (1990-2000). Acta Obstet Gynecol Scand 2003; 82: 229–34PubMedCrossRefGoogle Scholar
  54. 54.
    Chung RT, Andersen J, Volberding P, et al. Peginterferon alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons. N Engl J Med 2004; 351: 451–9PubMedCrossRefGoogle Scholar
  55. 55.
    Resti M, Azzari C, Bortolotti F. Hepatitis C virus infection in children coinfected with HIV: epidemiology and managment. Pediatr Drugs 2002; 4: 571–80Google Scholar
  56. 56.
    Piliero PJ, Faragon JJ. Hepatitis B virus and HIV coinfection. AIDS Read 2002; 12: 443–51PubMedGoogle Scholar
  57. 57.
    Centers for Disease Control and Prevention. 1999 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus: U.S. Public Health Service (USPHS) and Infectious Diseases Society of America (IDSA). Morbidity and Mortality Weekly Report 1999; 48RR 10: 1–59Google Scholar
  58. 58.
    Chui DW, Owen RL. AIDS and the gut. J Gastroenterol Hepatol 1994; 9: 291–303PubMedCrossRefGoogle Scholar
  59. 59.
    Montessori V, Harris M, Montaner JS. Hepatotoxicity of nucleoside reverse transcriptase inhibitors. Semin Liver Dis 2003; 23: 167–72PubMedCrossRefGoogle Scholar
  60. 60.
    Dieterich DT. Long-term complications of nucleoside reverse transcriptase inhibitor therapy. AIDS Read 2003; 13: 176–84PubMedGoogle Scholar
  61. 61.
    Carroccio A, Guarino A, Zuin G, et al. Efficacy of oral pancreatic enzyme therapy for the treatment of fat malabsorption in HIV-infected patients. Aliment Pharmacol Ther 2001; 15: 1619–25PubMedCrossRefGoogle Scholar
  62. 62.
    Beisel WR. Nutrition and immune function: overview. J Nutr 1996; 126: 2611S–5SPubMedGoogle Scholar
  63. 63.
    Heller L, Fox S, Hell KJ, et al. Development of an instrument to assess nutritional risk factors for children with human immunodeficiency virus. J Am Diet Assoc 2000; 100: 323–9PubMedCrossRefGoogle Scholar
  64. 64.
    Miller TL. Nutritional aspects of HIV-infected children receiving highly active antiretroviral therapy. AIDS 2003; 17Suppl. 1: S130–40PubMedCrossRefGoogle Scholar
  65. 65.
    Johann-Liang R, O’Neill L, Cervia J, et al. Energy balance, viral burden, insulin-like growth factor-1, interleukin 6 and growth impairment in children infected with human immunodeficiency virus. AIDS 2000; 14: 683–90PubMedCrossRefGoogle Scholar
  66. 66.
    Miller TL. Nutrition in paediatric human immunodeficiency virus infection. Proc Nutr Soc 2000; 59: 155–62PubMedCrossRefGoogle Scholar
  67. 67.
    Miller TL, Mawn BE, Orav J, et al. The effect of protease inhibitor therapy on growth and body composition in human immunodeficiency virus type 1-infected children. Pediatrics 2001; 107: e77PubMedCrossRefGoogle Scholar
  68. 68.
    Clarick RH, Hanekom WA, Yogev R, et al. Megestrol acetate treatment of growth failure in children infected with human immunodeficiency virus. Pediatrics 1997; 99: 354–7PubMedCrossRefGoogle Scholar
  69. 69.
    Goulet O, Colomb V. Enteral nutrition. In: Guandalini S, editor. Textbook of pediatric gastroenterology. London: Martin Dunitz Ltd, 2004: 539–54Google Scholar
  70. 70.
    Guarino A, Spagnuolo MI, Giacomet V, et al. Effects of nutritional rehabilitation on intestinal function and on CD4 cell number in children with HIV. J Pediatr Gastroenterol Nutr 2002; 34: 366–71PubMedCrossRefGoogle Scholar
  71. 71.
    Villamor E, Mbise R, Spegelman D, et al. Vitamin A supplements ameliorate the adverse effects of HIV-1, malaria, and diarrheal infections on child growth. Pediatrics 2002; 109: e6PubMedCrossRefGoogle Scholar
  72. 72.
    Duggan C, Fawzie W. Micronutrients and child health: studies in international nutrition and HIV infection. Nutr Rev 2001; 59: 358–69PubMedCrossRefGoogle Scholar
  73. 73.
    Carr A, Cooper DA. Adverse effects of antiretroviral therapy. Lancet 2000; 356: 1423–30PubMedCrossRefGoogle Scholar
  74. 74.
    Sulkowski MS, Thomas DL, Mehta SH, et al. Hepatotoxicity associated with nevirapine or efavirenz-containing antiretroviral therapy: role of hepatitis C and B infections. Hepatology 2002; 35: 182–9PubMedCrossRefGoogle Scholar
  75. 75.
    Butler KM, Venzon D, Henry N, et al. Pancreatitis in human immunodeficiency virus-infected children receiving dideoxyinosine. Pediatrics 1993; 91: 747–51PubMedGoogle Scholar
  76. 76.
    The Division of Microbiology and Infectious Diseases (DMID). Pediatric toxicity tables [online]. Available from URL: pp. 60–70 [Accessed 2003 Mar 6]
  77. 77.
    Ammassari A, Murri R, Pezzotti P, et al. Self-reported symptoms and medication side effects influence adherence to highly active antiretroviral therapy in persons with HIV infection. J Acquir Immune Defic Syndr 2001; 28: 445–9PubMedGoogle Scholar
  78. 78.
    McCabe RP. Gastrointestinal manifestations of non-AIDS immunodeficiency. Curr Treat Options Gastroenterol 2002; 5: 17–25PubMedCrossRefGoogle Scholar
  79. 79.
    Wittenberg D, Benitez CV, Canani RB, et al. HIV infection: Working Group Report of the Second World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr 2004; 39: S640–6PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  • Alfredo Guarino
    • 1
  • Eugenia Bruzzese
    • 1
  • Giulio De Marco
    • 1
  • Vittoria Buccigrossi
    • 1
  1. 1.Department of PediatricsUniversity ‘Federico II’NaplesItaly

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