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  • Print publication year: 2009
  • Online publication date: January 2010

33 - Perinatal human immunodeficiency virus infection

from Section 4 - Specific conditions associated with fetal and neonatal brain injury

Summary

Introduction

Since the initial description of acquired immune deficiency syndrome (AIDS) cases in infants and children more than 25 years ago, the epidemiology of the pediatric human immunodeficiency virus type 1 (HIV-1) epidemic has changed significantly. Most pediatric HIV infections occur through perinatal transmission. Dramatic declines in the number of perinatally HIV infected children have been reported in the USA and Europe due to prompt implementation of strategies to prevent mother-to-child transmission of HIV (PMTCT). Further, availability of highly active antiretroviral therapy (HAART) has led to improved survival of HIV-infected children into adolescence and adulthood, changing most HIV infections into a chronic rather than an acute disease. In contrast, prevention of mother-to-child HIV transmission is a major public health challenge in many resource-limited countries. Although several effective, simple, and less expensive prophylactic antiretroviral regimens are available to prevent perinatal HIV transmission, these interventions have not been widely implemented in the developing world.

Pediatricians and obstetricians play a crucial role in the prevention of perinatal HIV transmission, including identification of HIV-infected women during pregnancy, treatment of the pregnant women with appropriate antiretroviral therapy, ensuring evaluation for HIV infection in early infancy, and subsequent provision of ongoing care for children and families affected by HIV. The purpose of this chapter is to review advances in the prevention of perinatal HIV transmission and highlight certain unique features of HIV infection in infants with a focus on early diagnosis, clinical manifestations, treatment, and prognosis.

References
,Centers for Disease Control. Unexplained immunodeficiency and opportunistic infections in infants: New York, New Jersey, California. MMWR 1982; 31: 665–7.
Prendergast, A, Tudor-Williams, G, Jeena, P, et al. International perspectives, progress, and future challenges of paediatric HIV infection. Lancet 2007; 370: 68–80.
Thorne, C, Newell, ML. HIV. Semin Fetal Neonatal Med 2007; 12: 174–81.
Shetty, AK, Maldonado, Y. Advances in the prevention of perinatal HIV-1 transmission. NeoReviews 2005; 6: 12–25.
Mofenson, LM. Advances in the prevention of vertical transmission of human immunodeficiency virus. Semin Pediatr Infect Dis 2003; 14: 295–308.
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: 1522–8.
King, SM. American Academy of Pediatrics Committee on Pediatric AIDS, American Academy of Pediatrics Infectious Diseases and Immunization Committee. Evaluation and treatment of the human immunodeficiency virus-1-exposed infant. Pediatrics 2004; 114: 497–505.
,American Academy of Pediatrics. Human immunodeficiency virus infection. In Pickering, LK, Baker, CJ, Long, SS, eds., Red Book: 2006 Report of the Committee on Infectious Diseases, 27th edn. Elk Grove Village, IL, American Academy of Pediatrics, 2006: 378–401.
Lindegren, ML, Steinberg, S, Byers, RH. Epidemiology of HIV/AIDS in children. Pediatr Clin N Am 2004; 47: 1–20.
,Centers for Disease Control and Prevention. Achievements in public health: reduction in perinatal transmission of HIV infection: United States, 1985–2005. MMWR Morb Mortal Wkly Rep 2006; 55: 592–7.
McKenna, MT, Hu, X. Recent trends in the incidence and morbidity that are associated with perinatal human immunodeficiency virus infection in the United States. Am J Obstet Gynecol 2007; 197: S10–16.
Brady, MT. Pediatric human immunodeficiency virus-1 infection. Adv Pediatr 2005; 52: 163–93.
,UNAIDS/World Health Organization. AIDS Epidemic Update, December, 2006. Geneva: UNAIDS, 2006.
Newell, ML, Coovadia, H, Cortina-Borja, M, et al. Ghent International AIDS Society (IAS) Working Group on HIV Infection in Women and Children. Mortality of infected and uninfected infants born to HIV-infected mothers in Africa: a pooled analysis. Lancet 2004; 364: 1236–43.
Kourtis, AP, Lee, FK, Abrams, EJ, et al. Mother-to-child transmission of HIV-1: timing and implications for prevention. Lancet Infect Dis 2006; 6: 726–32.
Fowler, MG, Newell, ML. Breastfeeding and HIV-1 transmission in resource-limited settings. J Acquir Immune Defic Syndr 2002; 30: 230–9.
Kourtis, AP, Jamieson, DJ, Vincenzi, I, et al. Prevention of human immunodeficiency virus-1 transmission to the infant through breastfeeding: new developments. Am J Obstet Gynecol 2007; 197: S113–22.
Thorne, C, Newell, ML. Prevention of mother-to-child transmission of HIV infection. Curr Opin Infect Dis 2004; 17: 247–52.
,Working Group on Mother-to-Child Transmission of HIV. Rates of mother-to-child transmission of HIV-1 in Africa, America and Europe: results from 13 perinatal studies. J Acquir Immune Defic Syndr Hum Retrovirol 1995; 8: 506–10.
Blanche, S, Rouzioux, C, Moscato, MLG, et al. A prospective study of infants born to women seropositive for human immunodeficiency virus type 1. N Engl J Med 1989; 320: 1643–8.
,European Collaborative Study. Children born to women with HIV-1 infection: natural history and risk of transmission. Lancet 1991; 337: 253–60.
Bryson, YJ, Luzuriaga, K, Sullivan, JL, et al. Proposed definitions for in utero versus intrapartum transmission of HIV-1. N Engl J Med 1992; 327: 1246–7.
Lewis, SH, Reynolds-Kohler, C, Fox, HE, et al. HIV-1 trophoblastic and villous Hofbauer cells, and haematological precursors in eight-week fetuses. Lancet 1990; 335: 565–8.
Lyman, WD, Kress, Y, Kure, K, et al. Detection of HIV in fetal central nervous system tissue. AIDS 1990; 4: 917–20.
Mano, H, Cherman, JC. Fetal human immunodeficiency virus type 1 infection of different organs in the second trimester. AIDS Res Hum Retroviruses 1991; 7: 83–8.
Newell, ML. Mechanisms and timing of mother-to-child transmission of HIV-1. AIDS 1998; 12: 831–7.
Rogers, MF, Ou, CY, Rayfield, M, et al. Use of the polymerase chain reaction for early detection of the proviral sequences of human immunodeficiency virus in infants born to seropositive mothers. N Engl J Med 1989; 320: 1649–54.
Weiblen, BJ, Lee, FK, Cooper, ER, et al. Early diagnosis of HIV infection in infants by detection of IgA HIV antibodies. Lancet 1990; 335: 988–90.
Quinn, TC, Kline, RL, Halsey, N, et al. Early diagnosis of perinatal HIV infection by detection of viral-specific IgA antibodies. JAMA 1991; 266: 3439–942.
Krivine, A, Firtion, G, Cao, L, et al. HIV replication during the first weeks of life. Lancet 1992; 339: 1187–9.
Goedert, JJ, Duliege, AM, Amos, CI, et al. High risk of HIV-1 infection for firstborn twins. Lancet 1991; 338: 1471–5.
,The International Perinatal HIV Group. The mode of delivery and the risk of vertical transmission of human immunodeficiency virus type 11: a meta-analysis of 15 prospective studies. N Engl J Med 1999; 340: 977–87.
,The European Mode of Delivery Collaboration. Elective cesarean section versus vaginal delivery in prevention of vertical HIV-1 transmission: a randomized clinical trial. Lancet 1999; 353: 1035–9.
Havens, PL, Waters, D. Management of the infant born to a mother with HIV infection. Pediatr Clin North Am 2004; 51: 909–37.
Garcia, P, Kalish, , Pitt, J, et al. Maternal levels of plasma human immunodeficiency virus type-1 RNA and the risk of perinatal transmission. N Engl J Med 1999; 341: 394–402.
Mofenson, LM, Lambert, JS, Stiehm, ER, et al. Risk factors for perinatal transmission of human immunodeficiency virus type 1 in women treated with zidovudine. N Engl J Med 1999; 341: 385–93.
Magder, LS, Mofenson, L, Paul, ME, et al. Risk factors for in utero and intrapartum transmission of HIV. J Acquir Immune Defic Syndr 2005; 38: 87–95.
Ioannidis, JPA, Abrams, EJ, Ammann, A, et al. Perinatal transmission of human immunodeficiency virus type 1 by pregnant women with RNA virus loads < 1000 copies/ml. J Infect Dis 2001; 183: 539–45.
O'Shea, S, Newell, ML, Dunn, D, et al. Maternal viral load, CD4 cell count and vertical transmission of HIV-1. J Med Virol 1998; 54: 113–17.
Mock, P, Shaffer, N, Bhadrakom, C, et al. Maternal viral load and timing of mother-to-child HIV transmission, Bangkok, Thailand. AIDS 1999; 13: 407–14.
St Louis, ME, Kamenga, M, Brown, C, et al. Risk for perinatal HIV-1 transmission according to maternal immunologic, virologic, and placental factors. JAMA 1993; 269: 2853–9.
Borkowsky, W, Krasinski, K, Cao, Y, et al. Correlation of perinatal transmission of human immunodeficiency virus type 1 with maternal viremia and lymphocyte phenotypes. J Pediatr 1994; 125: 345–51.
Sperling, RS, Shapiro, , Coombs, RW, et al. Maternal viral load, zidovudine treatment, and the risk of transmission of human immunodeficiency virus type 1 from mother to infant. N Engl J Med 1996; 335: 1621–9.
Newell, ML, Peckham, C. Risk factors for vertical transmission of HIV-1 and early markers of HIV-1 infection in children. AIDS 1993; 7: S591–7.
Gabiano, C, Tobo, PA, Martino, M, et al. Mother-to-child transmission of human immunodeficiency virus type 1: risk of infection and correlates of transmission. Pediatrics 1992; 90: 369–74.
Thomas, PA, Weedon, J, Krasinski, K, et al. Maternal predictors of perinatal human immunodeficiency virus transmission. Pediatr Infect Dis J 1994; 13: 489–95.
Mayers, MM, Davenny, K, Schoenbaum, EE, et al. A prospective study of infants of human immunodeficiency virus seropositive and seronegative women with a history of intravenous drug use or of intravenous drug-using sex partners, in the Bronx, New York City. Pediatrics 1991; 88: 1248–56.
,European Collaborative Study. Risk factors for mother-to-child transmission of HIV-1. Lancet 1992; 339: 1007–12.
Chuachoowong, R, Shaffer, N, Siriwasin, W, et al. Short-course antenatal zidovudine reduces both cervicovaginal human immunodeficiency virus type 1 RNA levels and risk of perinatal transmission. Bangkok Collaborative Perinatal HIV Transmission Study Group. J Infect Dis 2000; 181: 99–106.
Landesman, SH, Kalish, , Burns, D, et al. Obstetrical factors and the transmission of human immunodeficiency virus type 1 from mother to child. N Engl J Med 1996; 334: 1617–23.
,European Collaborative Study. Vertical transmission of HIV-1: maternal immune status and obstetric factors. AIDS 1996; 10: 1675–81.
Goedert, JJ, Mendez, H, Drummond, JE, et al. Mother-to-infant transmission of human immunodeficiency virus type 1: association with prematurity or low antigp120. Lancet 1989; 2: 1351–4.
Tovo, PA, Martino, M, Gabiano, C, et al. Mode of delivery and gestational age influence perinatal HIV-1 transmission. J Acquir Immune Defic Syndr Hum Retrovirol 1996; 11: 88–94.
Wolinsky, SM, Wike, CM, Korber, BTM, et al. Selective transmission of human immunodeficiency virus type-1 variants from mothers to infants. Science 1992; 255: 1134–7.
MacDonald, KS, Embree, J, Njenga, S, et al. Mother–child class I HLA concordance increases perinatal human immunodeficiency virus type 1 transmission. J Infect Dis 1998; 177: 551–6.
Kostrikis, LG. Impact of natural chemokine receptor polymorphisms on perinatal transmission of human immunodeficiency virus type 1. Teratology 2000; 61: 387–90.
John-Stewart, G, Mbori-Ngacha, D, Ekpini, R, et al. Breast-feeding and transmission of HIV-1. J Acquir Immune Defic Syndr 2004; 35: 196–202.
Coutsoudis, A, Dabis, F, Fawzi, W, et al. Late postnatal transmission of HIV-1 in breastfed children: an individual patient data meta-analysis. J Infect Dis 2004; 189: 2154–66.
Lewis, P, Nduati, RW, Kreiss, JK, et al. Cell-free HIV type 1 in breast milk. J Infect Dis 1998; 177: 34–9.
Koulinska, IN, Villamour, E, Chaplin, B, et al. Transmission of cell-free and cell-associated HIV-1 through breastfeeding. J Acquir Immune Defic Syndr 2006; 41: 93–9.
Dunn, DT, Newell, ML, Ades, AE, et al. Risk of human immunodeficiency virus type 1 transmission through breastfeeding. Lancet 1992; 340: 585–8.
Tess, BH, Rodrigues, LC, Newell, ML, et al. Breastfeeding, genetic, obstetric and other risk factors associated with mother-to-child transmission of HIV-1 in Sao Paulo State, Brazil. AIDS 1998; 12: 513–20.
Bobat, R, Moodley, D, Coutsoudis, A, et al. Breastfeeding by HIV-1 infected women and outcome in their infants: a cohort study from Durban, South Africa. AIDS 1997; 11: 1627–33.
Nduati, R, John, G, Mbori-Ngacha, D, et al. Effect of breastfeeding and formula feeding on transmission of HIV-1: a randomized controlled trial. JAMA 2000; 283: 1167–74.
Miotti, PG, Taha, TET, Kumwenda, NI, et al. HIV transmission through breastfeeding: a study in Malawi. JAMA 1999; 282: 744–9.
Bertolli, J, St Louis, ME, Simonds, RJ, et al. Estimating the timing of mother-to-child transmission of human immunodeficiency virus in a breast-feeding population in Kinshasa, Zaire. J Infect Dis 1996; 174: 722–6.
Epkini, ER, Wiktor, SZ, Satten, FA, et al. Late postnatal mother-to-child transmission of HIV-1 in Abidjan, Cote d'Ivoire. Lancet 1997; 349: 1054–9.
Leroy, V, Newell, ML, Dabis, F, et al. International multicentre pooled analysis of late postnatal mother-to-child transmission of HIV-1 infection. Lancet 1998; 352: 597–600.
Taha, TE, Hoover, DR, Kumwenda, NI, et al. Late postnatal transmission of HIV-1 and associated risk factors. J Infect Dis 2007; 196: 10–14.
Iliff, PJ, Piwoz, EG, Tacengwa, NV, et al. Early exclusive breastfeeding reduces the risk of postnatal HIV-1 transmission and increases HIV-free survival. AIDS 2005; 19: 699–708.
Coovadia, HM, Rollins, NC, Bland, RM, et al. Mother-to-child transmission of HIV-1 infection during exclusive breastfeeding in the first 6 months of life: an intervention cohort study. Lancet 2007; 369: 1107–16.
,Read JS and the Committee on Pediatric AIDS, American Academy of Pediatrics. Diagnosis of HIV-1 infection in children younger than 18 months in the United States. Pediatrics 2007; 120: 1547–62.
Owens, DK, Holodniy, M, McDonald, TW, et al. A meta-analytic evaluation of the polymerase chain reaction for the diagnosis of HIV infection in infants. JAMA 1996; 275: 1342–8.
Cunningham, CK, Charbonneau, TT, Song, K, et al. Comparison of human immunodeficiency virus 1 DNA polymerase chain reaction and qualitative and quantitative RNA polymerase chain reaction in human immunodeficiency virus 1-exposed infants. Pediatr Infect Dis J 1999; 18: 30–5.
Simonds, RJ, Brown, TM, Thea, DM, et al. Sensitivity and specificity of a qualitative RNA detection assay to diagnose HIV infection in young infants. Perinatal AIDS Collaborative Transmission Study. AIDS 1998; 12: 1545–9.
Rouet, F, Montcho, C, Rouzioux, C, et al. Early diagnosis of paediatric HIV-1 infection among African breast-fed children using a quantitative plasma HIV RNA assay. AIDS 2001; 15: 1849–56.
Young, NL, Shaffer, N, Chaowanachan, T, et al. Early diagnosis of HIV-1-infected infants in Thailand using RNA and DNA PCR assays sensitive to non-B subtypes. J Acquir Immune Defic Syndr 2000; 24: 401–7.
Luzuriaga, K, Wu, H, McManus, M, et al. Dynamics of human immunodeficiency virus type 1 replication in vertically infected infants. J Virol 1999; 73: 362–7.
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: 442–50.
Scott, GB, Hutto, C, Makuch, RW, et al. Survival in children with perinatally acquired human immunodeficiency virus type 1 infection. N Engl J Med 1989; 321: 1791–6.
Marion, RW, Wiznia, AA, Hutcheon, G, et al. Human T-cell lymphotropic virus type III (HTLV-III) embryopathy: a new dysmorphic syndrome associated with intrauterine HTLV-III infection. Am J Dis Child 1986; 140: 638–40.
Qazi, QH, Sheikh, TM, Fikrig, S, et al. Lack of evidence for craniofacial dysmorphism in perinatal human immunodeficiency virus infection. J Pediatr 1998; 112: 7–11.
Galli, L, deMartino, M, Tovo, PA, et al. Onset of clinical signs with HIV-1 perinatal infection. AIDS 1995; 9: 455–61.
Newell, ML, Peckham, C, Dunn, D, et al. Natural history of vertically-acquired human immunodeficiency virus-1 infection. The European Collaborative Study. Pediatrics 1994; 94: 815–19.
Mofenson, LM, Oleske, J, Serchuck, L, et al. Treating opportunistic infections among HIV-exposed and infected children: recommendations from CDC, the National Institutes of Health, and the Infectious Diseases Society of America. MMWR Recomm Rep 2004; 53: 1–92.
Pollack, H, Glasberg, H, Lee, E, et al. Impaired early growth of infants perinatally infected with human immunodeficiency virus: correlation with viral load. J Pediatr 1997; 130: 915–22.
Kline, MW. Vertically acquired human immunodeficiency virus infection. Semin Pedatr Infect Dis 1999; 10: 147–53.
,Centers for Disease Control. Revision of the CDC surveillance case definition for acquired immune deficiency syndrome. MMWR 1987; 36: 1–15.
,Centers for Disease Control and Prevention. 1994 revised classification system for human immunodeficiency virus infection in children less than 13 years of age. MMWR 1994; 43: 1–11.
Simonds, RJ, Oxtoby, MJ, Caldwell, MB, et al. Pneumocystis carinii pneumonia among US children with perinatally acquired HIV infection. JAMA 1993; 270: 470–3.
Rie, , Harrington, PR, Dow, A, et al. Neurologic and neurodevelopmental manifestations of pediatric HIV/AIDS: a global perspective. Eur J Paediatr Neurol 2007; 11: 1–9.
Gorry, PR, Bristol, G, Zack, JA, et al. Macrophage tropism of human immunodeficiency virus type 1 isolates from brain and lymphoid tissues predict neurotropism independent of coreceptor specificity. J Virol 2001; 75: 10073–89.
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. J Pediatr 1998; 132: 808–12.
Labato, MN, Caldwell, MB, Ng, P, et al. Encephalopathy in children with perinatally acquired human immunodeficiency virus infection. J Pediatr 1995; 126: 710–15.
Chiriboga, CA, Fleishman, S, Champion, S, et al. Incidence and prevalence of HIV encephalopathy in children with HIV infection receiving highly active anti-retroviral therapy (HAART). J Pediatr 2005; 146: 402–7.
Mitchell, CD. HIV-1 encephalopathy among perinatally infected children: neuropathogenesis and response to highly active antiretroviral therapy. Ment Retard Dev Disabil Res Rev 2006; 12: 216–22.
Kaul, M, Zheng, J, Okamoto, S, et al. HIV-1 infection and AIDS: consequences for the CNS. Cell Death Differ 2005; 12: 878–92.
Epstein, LG, Gelbard, HA. HIV-1-induced neuronal injury in the developing brain. J Leukoc Biol 1999; 65: 453–7.
Schwartz, L, Major, EO. Neural progenitors and HIV-1-associated central nervous system disease in adults and children. Curr HIV Res 2006; 4: 319–27.
Lyman, YD, Kress, Y, Kure, K, et al. Detection of HIV in fetal central nervous tissue. AIDS 1990; 4: 917–20.
Kozlowski, PB, Brudkowska, J, Kraszpulski, M, et al. Microencephaly in children congenitally infected with human immunodeficiency virus: a gross-anatomical morphometric study. Acta Neuropathol (Berl) 1997; 93: 136–45.
Levy, JA, Shimabukuro, J, Hollander, H, et al. Isolation of AIDS-associated retroviruses from cerebrospinal fluid and brain of patients with neurological symptoms. Lancet 1985; 2: 586–8.
Shaw, GM, Harper, ME, Hahn, BH, et al. HTLV-III infection in brains of children and adults with AIDS encephalopathy. Science 1985; 227: 177–82.
Hollander, H, Levy, JA. Neurologic abnormalities and recovery of human immunodeficiency virus from cerebrospinal fluid. Ann Intern Med 1987; 106: 692–5.
Belman, AL. Pediatric neuro-AIDS: update. Neuroimaging Clin North Am 1997; 7: 593–613.
Brouwers, P, Carli, C, Civitello, L, et al. Correlation between computed tomographic brain scan abnormalities and neuropsychological function in children with symptomatic human immunodeficiency virus disease. Arch Neurol 1995; 52: 39–44.
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: 808–12.
Belman, AL, Ultmann, MH, Horoupian, D, et al. Neurologic complications in infants and children with acquired immune deficiency syndrome. Ann Neurol 1985; 18: 560–6.
Epstein, LG, Sharer, LR, Oleske, JM, et al. Neurologic manifestations of human immunodeficiency virus infection in children. Pediatrics 1986; 78: 678–87.
Raskino, C, Pearson, DA, Baker, CJ, et al. Neurologic, neurocognitive and brain growth outcomes in human immunodeficiency virus-infected children receiving different nucleoside antiretroviral regimens. Pediatrics 1999; 104: e32.
Tardieu, M, Chenadec, J, Persoz, A, et al. HIV-1 related encephalopathy in infants compared with children and adults. French Pediatric HIV Infection Study and the SEROCO Group. Neurology 2000; 54: 1089–95.
,Centers for Disease Control and Prevention. HIV/AIDS Surveillance Report. Atlanta, GA: CDC, 1993.
Johann-Liang, R, Lin, K, Cervia, J, et al. Neuroimaging findings in children perinatally infected with the human immunodeficiency virus. Pediatr Infect Dis J 1998; 17: 753–4.
Brouwers, P, Tudor-Williams, G, DeCarli, C, et al. Relation between stage of disease and neurobehavioral measures in children with symptomatic HIV disease. AIDS 1995; 9: 713–20.
Nozyce, M, Hittelman, J, Muenz, L, et al. Effect of perinatally acquired human immunodeficiency virus infection on neurodevelopment in children during the first two years of life. Pediatrics 1994; 94: 883–91.
Belman, AL, Muenz, LR, Marcus, JC, et al. Neurologic status of human immunodeficiency virus 1-infected infants and their controls: a prospective study from birth to 2 years. Mothers and Infants Cohort Study. Pediatrics 1996; 98: 1109–18.
Smith, R, Malee, K, Leighty, R, et al. Women and Infants Transmission Study Group. Effects of perinatal HIV infection and associated risk factors on cognitive development among young children. Pediatrics 2006; 117: 851–62.
Mintz, M. Clinical features and treatment interventions for human immunodeficiency virus-associated neurologic disease in children. Semin Neurol 1999; 19: 165–76.
Sanchez-Ramon, S, Resino, S, Bellon Cano, JM, et al. Neuroprotective effects of early antiretrovirals in vertical HIV infection. Pediatr Neurol 2003; 29: 218–21.
Saavedra-Lozano, J, Ramos, JT, Sanz, F, et al. Salvage therapy with abacavir and other reverse transcriptase inhibitors for human immunodeficiency-associated encephalopathy. Pediatr Infect Dis J 2006; 25: 1142–52.
DeCarli, C, Fugate, L, Falloon, J, et al. Brain growth and cognitive improvement in children with human immunodeficiency virus-induced encephalopathy after 6 months of continuous infusion zidovudine therapy. J Acquir Immune Defic Syndr 1991; 4: 585–92.
Pizzo, PA, Eddy, J, Falloon, J, et al. Effect of continuous intravenous infusion of zidovudine (AZT) in children with symptomatic HIV infection. N Engl J Med 1988; 319: 889–96.
Portegies, P. HIV-1, the brain, and combination therapy. Lancet 1995; 346: 1244–5.
McCoig, C, Castrejon, MM, Castano, E, et al. Effects of combination antiretroviral therapy on cerebrospinal fluid HIV RNA, HIV resistance, and clinical manifestations of encephalopathy. J Pediatr 2002; 141: 36–44.
Berk, DR, Falkovitz-Halpern, MS, Hill, DW. Temporal trends in early clinical manifestations of perinatal HIV infection in a population-based cohort. JAMA 2005; 293: 2221–31.
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: 190–7.
,Working Group on Antiretroviral Therapy and Medical Management of HIV-infected Children. Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. Rockville, MD: AIDSInfo, 2005. aidsinfo.nih.gov. Accessed March, 2008.
Sharland, N, di Zub, GC, Ramos, JT, et al. PENTA guidelines for the use of antiretroviral therapy in paediatric HIV infection. HIV Med 2002; 3: 215–26.
Abrams, EJ, Kuhn, L. Should treatment be started among all HIV-infected children and then stopped?Lancet 2003; 362: 1595–6.
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: 116–22.
Diaz, C, Hanson, C, Cooper, ER, et al. Disease progression in a cohort of infants with vertically acquired HIV infection observed from birth: the Women and Infants Transmission Study (WITS). J Acquir Immune Defic Syndr Hum Retrovirol 1998; 18: 221–8.
Anabwani, GM, Woldetsadik, EA, Kline, MW. Treatment of human immunodeficiency virus (HIV) in children using antiretroviral drugs. Semin Pediatr Infect Dis 2005; 16: 116–24.
Luzuriaga, K, McManus, M, Mofenson, LM, et al. A trial of three antiretroviral regimens in HIV-1 infected children. N Engl J Med 2004; 350: 2471–80.
Luzuriaga, K, Bryson, Y, Krogstad, P, et al. Combination treatment with zidovudine, didanosine, and nevirapine in infants with human immunodeficiency virus type 1 infection. N Engl J Med 1997; 336: 1343–9.
Luzuriaga, K, McManus, M, Catalina, M, et al. Early therapy of vertical human immunodeficiency virus type 1 (HIV-1) infection: control of viral replication and absence of persistent HIV-1 specific immune responses. J Virol 2000; 74: 6984–91.
Hainaut, M, Peltier, CA, Gerard, M, et al. Effectiveness of antiretroviral therapy initiated before the age of 2 months in infants vertically infected with human immunodeficiency virus type 1. Eur J Pediatr 2000; 159: 778–82.
Faye, A, Bertone, C, Teglas, JP, et al. Early multitherapy including a protease inhibitor for human immunodeficiency virus type 1 infected infants. Pediatr Infect Dis J 2002; 21: 518–25.
,Paediatric European Network for Treatment of AIDS (PENTA). Highly active antiretroviral therapy started in infants under 3 months of age: 72 week follow-up for CD4 cell count, viral load and drug resistance outcome. AIDS 2004; 18: 237–45.
Litalien, C, Faye, A, Compagnucci, A, et al. Pharmacokinetics of nelfinavir and its active metabolite, hydroxyl-tert-butylamide, in infants less than 1 year old perinatally infected with HIV-1. Pediatr Infect Dis J 2003; 22: 48–56.
Hoody, DW, Fletcher, CV. Pharmacology considerations for antiretroviral therapy in human immunodeficiency virus (HIV)-infected children. Semin Pediatr Infect Dis 2003; 14: 286–94.
McKinney, RE, Cunningham, CK. Newer treatment for HIV in children. Curr Opin Pediatr 2004; 16: 76–9.
Blanche, S, Tardieu, M, Duliege, AA, et al. Longitudinal study of 94 symptomatic infants with perinatally acquired human immunodeficiency virus infection. Am J Dis Child 1990; 144: 1210–14.
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: 442–50.
Thorne, C, Newell, ML, Botet, FA, et al. Older children and adolescents surviving with vertically acquired infection. J AIDS 2002; 29: 396–401.
Lambert, G, Thea, DM, Pliner, V, et al. Effect of maternal CD4+ cell count, acquired immune deficiency syndrome, and viral load on disease progression in infants with perinatally acquired human immunodeficiency virus type 1 infection. J Pediatr 1997; 130: 830–7.
Abrams, EJ, Wiener, J, Carter, R, et al. Maternal health factors and early pediatric antiretroviral therapy influence the rate of perinatal HIV-1 disease progression in children. AIDS 2003; 17: 867–77.
Rich, KC, Fowler, MG, Mofenson, LM, et al. Maternal and infant factors predicting disease progression in human immunodeficiency virus type 1-infected infants. Pediatrics 2000; 105: e8.
Maldonado, Y. Acquired immunodeficiency syndrome in the infant. In Remington, JS, Klein, JO, Wilson, C, et al. eds., Infectious Diseases of the Fetus and Newborn Infant, 6th edn. Philadelphia, PA: Saunders, 2006: 667–92.
Connor, EM, Sperling, RS, Gelber, R, et al. Reduction of maternal–infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. N Engl J Med 1994; 331: 1173–80.
Cooper, E, Charurat, M, Mofenson, L, et al. Combination antiretroviral strategies for the treatment of pregnant HIV-1 infected women and prevention of perinatal HIV-1 transmission. J Acquir Immune Defic Syndr 2002; 29; 484–94.
,Centers for Disease Control and Prevention. U.S. Public Health Service Task Force recommendations for use of antiretroviral drugs in pregnant women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States. MMWR Recomm Rep 2002; 51: 1–40.
Shaffer, N, Chuachoowong, R, Mock, PA, et al. Short-course zidovudine for perinatal HIV-1 transmission in Bangkok, Thailand: a randomized controlled trial. Lancet 1999; 353: 773–80.
Bardeguez, AD, Shapiro, , Mofenson, LM, et al. Effect of cessation of zidovudine prophylaxis to reduce vertical transmission on maternal HIV disease progression and survival. J Acquir Immune Defic Syndr 2003; 32: 170–81.
Wade, NA, Birkhead, GS, Warren, BL, et al. Abbreviated regimens of zidovudine prophylaxis and perinatal transmission of the human immunodeficiency virus. N Engl J Med 1998; 339: 1409–14.
Fowler, MG, Lamper, MA, Jamieson, DJ, et al. Reducing the risk of mother-to-child human immunodeficiency virus transmission: past successes, current progress and challenges, and future directions. Am J Obstet Gynecol 2007; 197: S3–9.
Bulterys, M, Jamieson, DJ, O'Sullivan, MJ, et al. Rapid HIV-1 testing during labor: a multicenter study. JAMA 2004; 292: 219–23.
Wilfert, CM, Stringer, JS. Prevention of pediatric human immunodeficiency virus. Semin Pediatr Infect Dis 2004; 15: 190–8.
Mofenson, LM. Successes and challenges in the perinatal HIV-1 epidemic in the United States as illustrated by the HIV-1 serosurvey of childbearing women. Arch Pediatr Adolesc Med 2004; 158: 422–5.
Shetty, AK, Maldonado, M. Preventing mother-to-child transmission of human immunodeficiency virus type 1 in resource-poor countries. Pediatr Infect Dis J 2003; 22: 553–5.
Gallo, RC. The end or the beginning of the drive to an HIV-preventive vaccine: a view from over 20 years. Lancet 2005; 366: 1894–8.
Drew, RS, Makufa, C, Foster, G. Strategies for providing care and support to children orphaned by AIDS. AIDS Care 1998; 10: S9–15.