Current Infectious Disease Reports

, Volume 5, Issue 6, pp 521–530 | Cite as

Management of antiretroviral therapy in neonates, children, and adolescents

  • Michael Neely
  • Andrea Kovacs
Article

Abstract

There have been tremendous advances in the prevention of mother-to-child transmission of HIV and treatment of HIVinfected children and adolescents. Although multiple classes of anti-HIV drugs are available that can control viral replication and stabilize immune function when used in combination, patients and their providers also must manage complex and frequently toxic regimens. This article summarizes official National Institutes of Health guidelines for the prevention of perinatal HIV infection and the management of pediatric and adolescent HIV infection, and provides the most current updates on indications for therapy, recommended first-line therapy, criteria for changing therapy, salvage therapy, and novel management strategies.

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References and Recommended Reading

  1. 1.
    AIDS epidemic update: December 2002, Joint United Nations Programme on HIV/AIDS (UNAIDS) and World Health Organization (WHO). http://www.who.int/hiv/facts/ epiupdate_en.pdf. Accessed August 29, 2003.Google Scholar
  2. 2.
    Bulterys M, Nolan ML, Jamieson D: Advances in the prevention of mother-to-child HIV-1 transmission: current issues, future challenges. AIDScience 2002.Google Scholar
  3. 3.
    Young people at risk: HIV/AIDS among America’s youth. Centers for Disease Control. http://www.cdc.gov/hiv/pubs/ facts/youth.htm. Accessed August 29, 2003.Google Scholar
  4. 4.
    Guidelines for the use of antiretroviral agents in pediatric HIV infection, US Department of Health and Human Services. http://www.aidsinfo.nih.gov. Accessed August 29, 2003. These are consensus guidelines for the comprehensive management of pediatric HIV infection.Google Scholar
  5. 5.
    Burns DN, Mofenson LM: Paediatric HIV-1 infection. Lancet 1999, 354(Suppl 2):SII1-SII6.PubMedCrossRefGoogle Scholar
  6. 6.
    Cooper ER, 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, 29:484–494.PubMedGoogle Scholar
  7. 7.
    Connor EM, Sperling RS, Gelber R, et al.: Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med 1994, 331:1173–1180.PubMedCrossRefGoogle Scholar
  8. 8.
    Cooper ER, Nugent RP, Diaz C, et al.: After AIDS clinical trial 076: the changing pattern of zidovudine use during pregnancy, and the subsequent reduction in the vertical transmission of human immunodeficiency virus in a cohort of infected women and their infants. Women and Infants Transmission Study Group. J Infect Dis 1996, 174:1207–1211.PubMedGoogle Scholar
  9. 9.
    Dorenbaum A, Cunningham CK, Gelber RD, et al.: Two-dose intrapartum/newborn nevirapine and standard antiretroviral therapy to reduce perinatal HIV transmission: a randomized trial. JAMA 2002, 288:189–198.PubMedCrossRefGoogle Scholar
  10. 10.
    Mofenson LM, Lambert JS, Stiehm ER, et al.: Risk factors for perinatal transmission of human immunodeficiency virus type 1 in women treated with zidovudine. Pediatric AIDS Clinical Trials Group Study 185 Team. N Engl J Med 1999, 341:385–393.PubMedCrossRefGoogle Scholar
  11. 11.
    Johnson VA, Petropoulos CJ, Woods CR, et al.: Vertical transmission of multidrug-resistant human immunodeficiency virus type 1 (HIV-1) and continued evolution of drug resistance in an HIV-1-infected infant. J Infect Dis 2001, 183:1688–1693.PubMedCrossRefGoogle Scholar
  12. 12.
    Eshleman SH, Becker-Pergola G, Deseyve M, et al.: Impact of human immunodeficiency virus type 1 (hiv-1) subtype on women receiving single-dose nevirapine prophylaxis to prevent hiv-1 vertical transmission (hiv network for prevention trials 012 study). J Infect Dis 2001, 184:914–917.PubMedCrossRefGoogle Scholar
  13. 13.
    Cunningham CK, Chaix ML, Rekacewicz C, et al.: Development of resistance mutations in women receiving standard antiretroviral therapy who received intrapartum nevirapine to prevent perinatal human immunodeficiency virus type 1 transmission: a substudy of pediatric AIDS clinical trials group protocol 316. J Infect Dis 2002, 186:181–188.PubMedCrossRefGoogle Scholar
  14. 14.
    Eshleman SH, Mracna M, Guay LA, et al.: Selection and fading of resistance mutations in women and infants receiving nevirapine to prevent HIV-1 vertical transmission (HIVNET 012). AIDS 2001, 15:1951–1957.PubMedCrossRefGoogle Scholar
  15. 15.
    Kovacs A, Husson R, Cowles K, et al.: Genotypic resistance to zidovudine and didanosine among early treated infants in ACTG 239 [abstract]. Proceedings of the 39th Annual Meeting of Infectious Diseases Society of America. San Francisco: October 2001.Google Scholar
  16. 16.
    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, 339:1409–1414.PubMedCrossRefGoogle Scholar
  17. 17.
    Petra Study Team: Efficacy of three short-course regimens of zidovudine and lamivudine in preventing early and late transmission of HIV-1 from mother to child in Tanzania, South Africa, and Uganda (Petra study): a randomised, double-blind, placebo-controlled trial. Lancet 2002, 359:1178–1186.CrossRefGoogle Scholar
  18. 18.
    Lallemant M, Jourdain G, Le Coeur S, et al.: A trial of shortened zidovudine regimens to prevent mother-to-child transmission of human immunodeficiency virus type 1. Perinatal HIV Prevention Trial (Thailand) Investigators. N Engl J Med 2000, 343:982–991.PubMedCrossRefGoogle Scholar
  19. 19.
    Guay LA, Musoke P, Fleming T, et al.: Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial. Lancet 1999, 354:795–802.PubMedGoogle Scholar
  20. 20.
    Moodley D, Moodley J, Coovadia H, et al.: A multicenter randomized controlled trial of nevirapine versus a combination of zidovudine and lamivudine to reduce intrapartum and early postpartum mother-to-child transmission of human immunodeficiency virus type 1. J Infect Dis 2003, 187:725–735.PubMedCrossRefGoogle Scholar
  21. 21.
    Jackson JB, Musoke P, Fleming T, et al.: Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: 18-month follow-up of the HIVNET 012 randomised trial. Lancet 2003, 362:859–868.PubMedCrossRefGoogle Scholar
  22. 22.
    Mirochnick M: Antiretroviral pharmacology in pregnant women and their newborns. Ann NY Acad Sci 2000, 918:287–297.PubMedCrossRefGoogle Scholar
  23. 23.
    Yuasa S, Sadakata Y, Takashima H, et al.: Selective and synergistic inhibition of human immunodeficiency virus type 1 reverse transcriptase by a non-nucleoside inhibitor, MKC-442. Mol Pharmacol 1993, 44:895–900.PubMedGoogle Scholar
  24. 24.
    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, 74:6984–6991.PubMedCrossRefGoogle Scholar
  25. 25.
    Bryson Y, Stek A, Mirochnick M, et al.: Pharmacokinetics (PK) antiviral activity and safety of nelfinavir (NFV) with ZDV/3TC in pregnant HIV-infected women and their infants: PACTG 353 cohort 2 [abstract]. Proceedings of the 9th Conference on Retrovirus and Opportunistic Infections. 2002.Google Scholar
  26. 26.
    Havlir DV, Tierney C, Friedland GH, et al.: In vivo antagonism with zidovudine plus stavudine combination therapy. J Infect Dis 2000, 182:321–325.PubMedCrossRefGoogle Scholar
  27. 27.
    Cao Y, Krogstad P, Korber BT, et al.: Maternal HIV-1 viral load and vertical transmission of infection: the ariel project for the prevention of HIV transmission from mother to infant. Nat Med 1997, 3:549–552.PubMedCrossRefGoogle Scholar
  28. 28.
    Eastman PS, Shapiro DE, Coombs RW, et al.: Maternal viral genotypic zidovudine resistance and infrequent failure of zidovudine therapy to prevent perinatal transmission of human immunodeficiency virus type 1 in pediatric AIDS. J Infect Dis 1998, 177:557–564.PubMedGoogle Scholar
  29. 29.
    Palumbo P, Holland B, Dobbs T, et al.: Antiretroviral resistance mutations among pregnant human immunodeficiency virus type 1-infected women and their newborns in the United States: vertical transmission and clades. J Infect Dis 2001, 184:1120–1126.PubMedCrossRefGoogle Scholar
  30. 30.
    Nolan M, Fowler MG, Mofenson LM: Antiretroviral prophylaxis of perinatal HIV-1 transmission and the potential impact of antiretroviral resistance. J Acquir Immune Defic Syndr 2002, 30:216–229.PubMedGoogle Scholar
  31. 31.
    Kourtis AP, Ibegbu C, Nahmias AJ, et al.: Early progression of disease in HIV-infected infants with thymus dysfunction. N Engl J Med 1996, 335:1431–1436. [Published erratum appears in N Engl J Med 1997, 336:595].PubMedCrossRefGoogle Scholar
  32. 32.
    Mofenson LM, Korelitz J, Meyer WA, et al.: The relationship between serum human immunodeficiency virus type 1 (HIV-1) RNA level, CD4 lymphocyte percent, and long-term mortality risk in HIV-1-infected children. National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group. J Infect Dis 1997, 175:1029–1038.PubMedCrossRefGoogle Scholar
  33. 33.
    Palumbo PE, Raskino C, Fiscus S, et al.: Predictive value of quantitative plasma HIV RNA and CD4+ lymphocyte count in HIVinfected infants and children. JAMA 1998, 279:756–761.PubMedCrossRefGoogle Scholar
  34. 34.
    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, 14:442–450.PubMedGoogle Scholar
  35. 35.
    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, 321:1791–1796.PubMedCrossRefGoogle Scholar
  36. 36.
    Kovacs A, Frederick T, Church J, et al.: CD4 T-lymphocyte counts and Pneumocystis carinii pneumonia in pediatric HIV infection. JAMA 1991, 265:1698–1703.PubMedCrossRefGoogle Scholar
  37. 37.
    Kovacs A, Schluchter M, Easley K, et al.: Cytomegalovirus infection and HIV-1 disease progression in infants born to HIV-1-infected women. Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection Study Group. N Engl J Med 1999, 341:77–84.PubMedCrossRefGoogle Scholar
  38. 38.
    1994 revised classification system for human immunodeficiency in virus infection in children less than 13 years of age. Centers for Disease Control and Prevention. MMWR Morb Mortal Wkly Rep 1994, 43:1–9.Google Scholar
  39. 39.
    Frederick T, Mascola L, Eller A, et al.: Progression of human immunodeficiency virus disease among infants and children infected perinatally with human immunodeficiency virus or through neonatal blood transfusion. Los Angeles County Pediatric AIDS Consortium and the Los Angeles County-University of Southern California Medical Center and the University of Southern California School of Medicine. Pediatr Infect Dis J 1994, 13:1091–1097.PubMedCrossRefGoogle Scholar
  40. 40.
    Spector SA: HIV therapy advances. Pediatric antiretroviral choices. AIDS 1994, 3(Suppl 8):S15-S18.CrossRefGoogle Scholar
  41. 41.
    Verweel G, Saavedra J, Ramilo O, de Groot R: Initiating HAART in HIV-1 infected children in Europe and the USA: clinical practice compared to guidelines and literature evidence [abstract]. Proceedings of the 2nd International AIDS Society Conference on HIV Pathogenesis and Treatment. 2003:S494.Google Scholar
  42. 42.
    US Department of Health and Human Services: Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. http://www.aidsinfo.nih.gov. Accessed August 29, 2003. These are consensus guidelines for the comprehensive management of HIV infection in adults and adolescents.Google Scholar
  43. 43.
    Mellors JW, Munoz A, Giorgi JV, et al.: Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med 1997, 126:946–954.PubMedGoogle Scholar
  44. 44.
    Sterling TR, Vlahov D, Lyles C, et al.: Sex differences in longitudinal human immunodeficiency virus type 1 RNA levels among seroconverters. J Infect Dis 1999, 180:666–672.PubMedCrossRefGoogle Scholar
  45. 45.
    Farzadegan H, Hoover DR, Astemborski J, et al.: Sex differences in HIV-1 viral load and progression to AIDS. Lancet 1998, 352:1510–1514.PubMedCrossRefGoogle Scholar
  46. 46.
    Burchett SK, Khoury M, McIntosh K, et al.: Viral load reduction (VLR) in children with advanced HIV disease treated with 4-drug antiretroviral treatment (ART) regimens including NRTIs, nevirapine (NVP), nelfinavir (NFV), and/or ritonavir (RTV) [abstract]. Proceedings of the 7th Conference on Retroviruses and Opportunistic Infections. 2000:206.Google Scholar
  47. 47.
    Wiznia A, Stanley K, Krogstad P, et al.: Combination nucleoside analog reverse transcriptase inhibitor(s) plus nevirapine, nelfinavir, or ritonavir in stable antiretroviral therapy-experienced HIV-infected children: week 24 results of a randomized controlled trial--PACTG 377. Pediatric AIDS Clinical Trials Group 377 Study Team. AIDS Res Hum Retroviruses 2000, 16:1113–1121.PubMedCrossRefGoogle Scholar
  48. 48.
    Krogstad P, Lee S, Johnson G, et al.: Nucleoside-analogue reversetranscriptase inhibitors plus nevirapine, nelfinavir, or ritonavir for pretreated children infected with human immunodeficiency virus type 1. Clin Infect Dis 2002, 34:991–1001.PubMedCrossRefGoogle Scholar
  49. 49.
    Nachman SA, Lindsey JC, Pelton S, et al.: Growth in human immunodeficiency virus-infected children receiving ritonavir-containing antiretroviral therapy. Arch Pediatr Adolesc Med 2002, 156:497–503.PubMedGoogle Scholar
  50. 50.
    Walmsley S, Bernstein B, King M, et al.: Lopinavir-ritonavir versus nelfinavir for the initial treatment of HIV infection. N Engl J Med 2002, 346:2039–2046.PubMedCrossRefGoogle Scholar
  51. 51.
    Saez-Llorens X, Violari A, Deetz CO, et al.: Forty-eight-week evaluation of lopinavir/ritonavir, a new protease inhibitor, in human immunodeficiency virus-infected children. Pediatr Infect Dis J 2003, 22:216–224.PubMedCrossRefGoogle Scholar
  52. 52.
    Starr SE, Fletcher CV, Spector SA, et al.: Combination therapy with efavirenz, nelfinavir, and nucleoside reverse-transcriptase inhibitors in children infected with human immunodeficiency virus type 1. Pediatric AIDS Clinical Trials Group 382 Team. N Engl J Med 1999, 341:1874–1881.PubMedCrossRefGoogle Scholar
  53. 53.
    Saavedra J, McCoig C, Mallory M, et al.: Clinical experience with triple nucleoside combination ZDV/3TC/Abacavir as initial therapy in HIV-infected children [abstract]. Proceedings of the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy. 2001:348.Google Scholar
  54. 54.
    Wells CJ, Sharland M, Smith CJ, et al.: Triple nucleoside analogue therapy with zidovudine, lamivudine and abacavir in the pediatric HIV London South Net (PHILS-NET) cohort [abstract]. Proceedings of the XIV International AIDS Conference. Barcelona: 2002:4625.Google Scholar
  55. 55.
    Department of Health and Human Services: Important interim results from a phase III, randomized, double-blind comparison of three protease-inhibitor-sparing regimens for the initial treatment of HIV infection (AACTG Protocol A5095). http://www.niaid.nih.gov/daids/pdf/aactg_a5095.pdf. Accessed July, 10 2003.Google Scholar
  56. 56.
    Saez-Llorens X VANDea: Once-daily emtricitabine in HIVinfected pediatric patients with other antiretroviral agents. [abstract]. Proceedings of the 10th Conference on Retroviruses and Opportunistic Infections. Boston: 2003:872.Google Scholar
  57. 57.
    McKinney R, Sea RMJ: PACTG 1021: an ongoing phase I/II study of once-daily emtricitabine, didanosine, and efavirenz in therapy-naive or minimally treated pediatric patients [abstract]. Proceedings of the 10th Conference on Retroviruses and Opportunistic Infections. Boston: 2003.Google Scholar
  58. 58.
    Wilson JW: Update on antiretroviral drug resistance testing: combining laboratory technology with patient care. AIDS Read 2003, 13:25–28.PubMedGoogle Scholar
  59. 59.
    Cohen NJ, Oram R, Elsen C, Englund JA: Response to changes in antiretroviral therapy after genotyping in human immunodeficiency virus-infected children. Pediatr Infect Dis J 2002, 21:647–653.PubMedCrossRefGoogle Scholar
  60. 60.
    Servais J, Hainaut M, Schmitz V, et al.: Resistance testing in children changing human immunodeficiency virus type 1 protease inhibitor. Pediatr Infect Dis J 2002, 21:214–220.PubMedCrossRefGoogle Scholar
  61. 61.
    Carpenter CC, Cooper DA, Fischl MA, et al.: Antiretroviral therapy in adults: updated recommendations of the International AIDS Society-USA Panel. JAMA 2000, 283:381–390.PubMedCrossRefGoogle Scholar
  62. 62.
    The EuroGUidelines Group for HIV resistance: Clinical and laboratory guidelines for the use of HIV-1 drug resistance testing as part of treatment management: recommendations for the European setting. AIDS 2001, 15:309–320.CrossRefGoogle Scholar
  63. 63.
    Little SJ, Daar ES, D’Aquila RT, et al.: Reduced antiretroviral drug susceptibility among patients with primary HIV infection. JAMA 1999, 282:1142–1149.PubMedCrossRefGoogle Scholar
  64. 64.
    Welles SL, Pitt J, Colgrove R, et al.: HIV-1 genotypic zidovudine drug resistance and the risk of maternal--infant transmission in the women and infants transmission study. The Women and Infants Transmission Study Group. AIDS 2000, 14:263–271.PubMedCrossRefGoogle Scholar
  65. 65.
    Nachman SA, Stanley K, Yogev R, et al.: Nucleoside analogs plus ritonavir in stable antiretroviral therapy-experienced HIV-infected children: a randomized controlled trial. Pediatric AIDS Clinical Trials Group 338 Study Team. JAMA 2000, 283:492–498.PubMedCrossRefGoogle Scholar
  66. 66.
    Starr SE, Fletcher CV, Spector SA, et al.: Efavirenz liquid formulation in human immunodeficiency virus-infected children. Pediatr Infect Dis J 2002, 21:659–663.PubMedCrossRefGoogle Scholar
  67. 67.
    Kovacs A, Burchett S, Khoury M, et al.: Virologic and immunologic responses in children with advanced HIV disease on a new HAART regimen [abstract]. Proceedings of the 8th Conference on Retroviruses and Opportunistic Infections. Chicago; 2001.Google Scholar
  68. 68.
    Church JA, Cunningham C, Hughes M, et al.: Safety and antiretroviral activity of chronic subcutaneous administration of T-20 in human immunodeficiency virus 1-infected children. Pediatr Infect Dis J 2002, 21:653–659.PubMedCrossRefGoogle Scholar
  69. 69.
    Badaro R, Dejesus CE, Lazzarin A, et al.: Efficacy and safety of atazanavir with ritonavir or saquinavir versus lopinavir/ ritonavir in combination with tenofovir and one NRTI in patients who have experienced virologic failure to multiple HAART regimens: 16-week results from BMS AI424-045 [abstract]. Proceedings of the 2nd International AIDS Society Conference on HIV Pathogenesis and Treatment. 2003:118.Google Scholar
  70. 70.
    Nieto-Cisneros I, Zala C, Fessel J, et al.: Antiviral efficacy, metabolic changes and safety of atazanavir (ATV) versus lopinavir/ ritonavir (LPV/RTV) in combination with 2 NRTIs in patients who have experienced virologic failure with prior picontaining regimen(s): 24-week results from BMS AI424-043 [abstract]. Proceedings of the 2nd International AIDS Society Conference on HIV Pathogenesis and Treatment. 2003:117.Google Scholar
  71. 71.
    Staszewski S, Dauer B, Von Hentig N, et al.: The LOPSAQ study: 24 week analysis of the double protease inhibitor (PI) salvage regimen containing lopinavir (LPV/R) plus saquinavir (SQV) without any additional antiretroviral (ART) therapy [abstract]. Proceedings of the 2nd International AIDS Society Conference on HIV Pathogenesis and Treatment. 2003:583.Google Scholar
  72. 72.
    Raguin G, Chene G, Morand-Joubert L, et al.: Salvage therapy with lopinavir/ritonavir, amprenavir +/- an additional boost with ritonavir: 1-year results of Puzzle 1-ANRS 104 Study [abstract]. Proceedings of the 2nd International AIDS Society Conference on HIV Pathogenesis and Treatment. 2003:585.Google Scholar
  73. 73.
    Low-Beer S, Yip B, O’Shaughnessy MV, et al.: Adherence to triple therapy and viral load response. J Acquir Immune Defic Syndr 2000, 23:360–361.PubMedGoogle Scholar
  74. 74.
    Jayaweera D, Tanner T, Nowak AM, et al.: Antiviral potency and tolerability of a convenient once a day direct observed therapy with amprenavir containing haart regimen in an antiretroviral naive, inner-city minority patients with poor HIV knowledge and very advanced AIDS. [abstract]. Proceedings from the International Conference on AIDS. 2002.Google Scholar
  75. 75.
    Jayaweera D, Tanner T, Nowak AM, et al.: Direct observed therapy (DOT) in HIV. Is it feasible in clinical practice? Problems associated with DOT an amprenavir containing HAART regimen in an antiretroviral naive, inner-city minority patient with poor HIV knowledge and very advanced AIDS [abstract]. Proceedings from the International Conference on AIDS. 2002.Google Scholar
  76. 76.
    Khanlou H, Kandula VR, Yeh V, et al.: Pilot study of directly observed therapy in highly nonadherent HIV-infected patients in an urban community-based institution. J Acquir Immune Defic Syndr 2003, 33:651–653.PubMedCrossRefGoogle Scholar
  77. 77.
    Mitty JA, Stone VE, Sands M, et al.: Directly observed therapy for the treatment of people with human immunodeficiency virus infection: a work in progress. Clin Infect Dis 2002, 34:984–990.PubMedCrossRefGoogle Scholar
  78. 78.
    Mitty JA, Macalino G, Taylor L, et al.: Directly observed therapy (DOT) for individuals with HIV: successes and challenges. Med Gen Med 2003, 5:30.CrossRefGoogle Scholar
  79. 79.
    Acosta EP, Gerber JG: Position paper on therapeutic drug monitoring of antiretroviral agents. AIDS Res Hum Retroviruses 2002, 18:825–834.PubMedCrossRefGoogle Scholar
  80. 80.
    Lori F, Foli A, Lisziewicz J: Structured treatment interruptions as a potential alternative therapeutic regimen for HIVinfected patients: a review of recent clinical data and future prospects. J Antimicrob Chemother 2002, 50:155–160.PubMedCrossRefGoogle Scholar
  81. 81.
    Ward DJ: Novel treatment strategies. Medscape 2003 8-26-0003. Ref Type: Electronic Citation.Google Scholar
  82. 82.
    Powderly WG, Saag MS, Chapman S, et al.: Predictors of optimal virological response to potent antiretroviral therapy. AIDS 1999, 13:1873–1880.PubMedCrossRefGoogle Scholar
  83. 83.
    Lawrence J, Mayers DL, Hullsiek KH, et al.: Structured treatment interruption in patients with multidrug-resistant human immunodeficiency virus. N Engl J Med 2003, 349:837–846.PubMedCrossRefGoogle Scholar
  84. 84.
    Katlama C, Dominguez S, Duvivier C, et al.: Long-term benefit of treatment interruption in salvage therapy (GIGHAART ANRS 097) [abstract]. Proceedings of the 10th Conference on Retroviruses and Opportunistic Infections. Boston: 2003.Google Scholar
  85. 85.
    Dybul M, Nies-Kraske E, Daucher M, et al.: A randomized controlled trial of long cycle structured intermittent versus continuous ARV therapy for chronic HIV infection [abstract]. Proceedings of the 10th Conference on Retroviruses and Opportunistic Infections. Boston: 2003.Google Scholar
  86. 86.
    Borkowsky W: YRMPea: T-cell and virologic outcomes of a progressively increasing structured treatment interruption study in chronically-infected children and adolescents. [abstract]. Proceedings from the 10th Conference on Retroviruses and Opportunistic Infections. Boston; 2003.Google Scholar
  87. 87.
    Leonard EG, McComsey GA: Metabolic complications of antiretroviral therapy in children. Pediatr Infect Dis J 2003, 22:77–84.PubMedCrossRefGoogle Scholar
  88. 88.
    Jaquet D, Levine M, Ortega-Rodriguez E, et al.: Clinical and metabolic presentation of the lipodystrophic syndrome in HIV-infected children. AIDS 2000, 14:2123–2128.PubMedCrossRefGoogle Scholar
  89. 89.
    McComsey GA, Alvarez A, Jet J: Is simplification of HAART safe in HIV-infected children? First pediatric switch study [abstract]. Proceedings from the 8th Conference on Retroviruses and Opportunistic Infections. 2001.Google Scholar
  90. 90.
    Church JA, Mitchell WG, Gonzalez-Gomez I, et al.: Mitochondrial DNA depletion, near-fatal metabolic acidosis, and liver failure in an HIV-infected child treated with combination antiretroviral therapy. J Pediatr 2001, 138:748–751.PubMedCrossRefGoogle Scholar
  91. 91.
    Blanche S, Tardieu M, Rustin P, et al.: Persistent mitochondrial dysfunction and perinatal exposure to antiretroviral nucleoside analogues. Lancet 1999, 354:1084–1089.PubMedCrossRefGoogle Scholar
  92. 92.
    Oleske J, Gaughan D, Mofenson L, et al.: Bone disorders in HIV-infected and -exposed children [abstract]. Proceedings from the XIV International AIDS Conference. Barcelona: 2002.Google Scholar

Copyright information

© Current Science Inc 2003

Authors and Affiliations

  • Michael Neely
  • Andrea Kovacs
    • 1
  1. 1.Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA

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