Leitlinie der Pädiatrische Arbeitsgemeinschaft AIDS (PAAD) e.V. zur antiretroviralen Therapie bei HIV-infizierten Kindern und Jugendlichen (2011)

Zusammenfassung

Die HIV-Infektion bei Kindern und Jugendlichen unterscheidet sich maßgeblich von der HIV-Infektion bei Erwachsenen. Dies spiegelt sich insbesondere im Infektionsmodus, in der viralen Dynamik bei unreifem Immunsystem und im klinischen Verlauf wider und beeinflusst unter anderem auch die Entwicklung des Kindes oder Jugendlichen. Neben virologischen, immunologischen und epidemiologischen Aspekten ist auch die psychosoziale Situation sehr unterschiedlich. Die genannten Aspekte und die Tatsache, dass deutlich weniger Wirkstoffe für die Therapie von Kindern zur Verfügung stehen, erfordern eigene Leitlinien für die HIV-Therapie bei Kindern und Jugendlichen. Die Pädiatrische Arbeitsgemeinschaft AIDS (PAAD) hat diese Leitlinie auf der Basis neuer Studienergebnisse, geänderter internationaler Leitlinien und neuer Arzneimittel 2011 aktualisiert.

Abstract

The HIV-infection in adults or children and adolescent differs substantially. Differences include the mode of infection, viral dynamics facing a developing immune system and the clinical course of the infection. In addition to the virological, immunological and epidemiological aspects the psychosocial situation is also very different. The above aspects and the decreased number of antiretroviral substances underline the need for specific guidelines for HIV-therapy in children and adolescents. The German Pediatric Working group AIDS (PAAD) has formulated this guideline in 2011 based on new study results, changes in international recommendations and newly available drugs.

Schlüsselwörter

pädiatrische HIV-Infektion - AIDS - antiretrovirale Therapie - Behandlungsleitlinien

Key words

pediatric HIV-infection - AIDS - antiretroviral therapy - treatment guidelines

• Literatur

• 1 Nucleoside exposure in the children of HIV-infected women receiving antiretroviral drugs: absence of clear evidence for mitochondrial disease in children who died before 5 years of age in five United States cohorts. J Acquir Immune Defic Syndr 2000; 25: 261-268
• 2 Comparison of dual nucleoside-analogue reverse-transcriptase inhibitor regimens with and without nelfinavir in children with HIV-1 who have not previously been treated: the PENTA 5 randomised trial. Lancet 2002; 359: 733-740
• 3 Pharmacokinetic study of once-daily versus twice-daily abacavir and lamivudine in HIV type-1-infected children aged 3–<36 months. Antivir Ther 2010; 15: 297-305
• 4 Aboulker JP, Babiker A, Chaix ML et al. 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: 237-245
• 5 Aslangul E, Assoumou L, Bittar R et al. Rosuvastatin versus pravastatin in dyslipidemic HIV-1-infected patients receiving protease inhibitors: a randomized trial. AIDS 2010; 24: 77-83
• 6 Babiker A, Castro nee Green H, Compagnucci A et al. First-line antiretroviral therapy with a protease inhibitor versus non-nucleoside reverse transcriptase inhibitor and switch at higher versus low viral load in HIV-infected children: an open-label, randomised phase 2/3 trial. Lancet Infect Dis 2011; 11: 273-283
• 7 Barret B, Tardieu M, Rustin P et al. Persistent mitochondrial dysfunction in HIV-1-exposed but uninfected infants: clinical screening in a large prospective cohort. AIDS 2003; 17: 1769-1785
• 8 Baxter JD, Mayers DL, Wentworth DN et al. A randomized study of antiretroviral management based on plasma genotypic antiretroviral resistance testing in patients failing therapy. CPCRA 046 Study Team for the Terry Beirn Community Programs for Clinical Research on AIDS. AIDS 2000; 14: F83-F93
• 9 Bergersen BM, Sandvik L, Bruun JN et al. Elevated Framingham risk score in HIV-positive patients on highly active antiretroviral therapy: results from a Norwegian study of 721 subjects. Eur J Clin Microbiol Infect Dis 2004; 23: 625-630
• 10 Bergshoeff A, Burger D, Verweij C et al. Plasma pharmacokinetics of once- versus twice-daily lamivudine and abacavir: simplification of combination treatment in HIV-1-infected children (PENTA-13). Antivir Ther 2005; 10: 239-246
• 11 Blanche S, Bologna R, Cahn P et al. Pharmacokinetics, safety and efficacy of darunavir/ritonavir in treatment-experienced children and adolescents. AIDS 2009; 23: 2005-2013
• 12 Bozzette SA, Ake CF, Tam HK et al. Cardiovascular and cerebrovascular events in patients treated for human immunodeficiency virus infection. N Engl J Med 2003; 348: 702-710
• 13 Brogly SB, Ylitalo N, Mofenson LM et al. In utero nucleoside reverse transcriptase inhibitor exposure and signs of possible mitochondrial dysfunction in HIV-uninfected children. AIDS 2007; 21: 929-938
• 14 Brunner J, Boehler T, Ehemann V et al. Decreased apoptosis despite severe CD4 depletion in the thymus of a human immunodeficiency virus-1 infected child. Klin Padiatrie 2011; 223: 246-248
• 15 Buchholz B, Hien S, Weichert S et al. Pediatric aspects of HIV1-infection – an overview. Minerva pediatrica 2010; 62: 371-387
• 16 Carr A, Miller J, Law M et al. A syndrome of lipoatrophy, lactic acidaemia and liver dysfunction associated with HIV nucleoside analogue therapy: contribution to protease inhibitor-related lipodystrophy syndrome. AIDS 2000; 14: F25-F32
• 17 Castro H, Judd A, Gibb DM et al. Risk of triple-class virological failure in children with HIV: a retrospective cohort study. Lancet 2011; 377: 1580-1587
• 18 Chene G, Angelini E, Cotte L et al. Role of long-term nucleoside-analogue therapy in lipodystrophy and metabolic disorders in human immunodeficiency virus-infected patients. Clin Infect Dis 2002; 34: 649-657
• 19 Cheseaux JJ, Jotterand V, Aebi C et al. Hyperlipidemia in HIV-infected children treated with protease inhibitors: relevance for cardiovascular diseases. J Acquir Immune Defic Syndr 2002; 30: 288-293
• 20 Church JA, Hughes M, Chen J et al. Long term tolerability and safety of enfuvirtide for human immunodeficiency virus 1-infected children. Pediatr Infect Dis J 2004; 23: 713-718
• 21 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
• 22 Cingolani A, Antinori A, Rizzo MG et al. Usefulness of monitoring HIV drug resistance and adherence in individuals failing highly active antiretroviral therapy: a randomized study (ARGENTA). AIDS 2002; 16: 369-379
• 23 Cohen CJ, Hunt S, Sension M et al. A randomized trial assessing the impact of phenotypic resistance testing on antiretroviral therapy. AIDS 2002; 16: 579-588
• 24 Croom KF, Keam SJ. Tipranavir: a ritonavir-boosted protease inhibitor. Drugs 2005; 65: 1669-1677 discussion 1669–1678
• 25 Daniels SR, Greer FR. Lipid screening and cardiovascular health in childhood. Pediatrics 2008; 122: 198-208
• 26 De Castro N, Braun J, Charreau I et al. Switch from enfuvirtide to raltegravir in virologically suppressed multidrug-resistant HIV-1-infected patients: a randomized open-label trial. Clin Infect Dis 2009; 49: 1259-1267
• 27 De Luca M, Miccinesi G, Chiappini E et al. Different kinetics of immunologic recovery using nelfinavir or lopinavir/ritonavir-based regimens in children with perinatal HIV-1 infection. Int J Immunopathol Pharmacol 2005; 18: 729-735
• 28 Delbeck D, Siepermann M, Feyen O et al. Terminally differentiated CD8 cells in HIV-infected children: HIV-GAG/POL specificity and IFN-gamma production. Klin Padiatr 2011; 223: 214-220
• 29 Dunn D. Short-term risk of disease progression in HIV-1-infected children receiving no antiretroviral therapy or zidovudine monotherapy: a meta-analysis. Lancet 2003; 362: 1605-1611
• 30 Dunn D, Woodburn P, Duong T et al. Current CD4 cell count and the short-term risk of AIDS and death before the availability of effective antiretroviral therapy in HIV-infected children and adults. J Infect Dis 2008; 197: 398-404
• 31 Durant J, Clevenbergh P, Halfon P et al. Drug-resistance genotyping in HIV-1 therapy: the VIRADAPT randomised controlled trial. Lancet 1999; 353: 2195-2199
• 32 European PLG. Antiretroviral therapy, fat redistribution and hyperlipidaemia in HIV-infected children in Europe. AIDS 2004; 18: 1443-1451
• 33 Farley J, Gona P, Crain M et al. Prevalence of elevated cholesterol and associated risk factors among perinatally HIV-infected children (4–19 years old) in Pediatric AIDS Clinical Trials Group 219C. J Acquir Immune Defic Syndr 2005; 38: 480-487
• 34 Farley JJ, Montepiedra G, Storm D et al. Assessment of adherence to antiretroviral therapy in perinatally HIV-infected children and youth using self-report measures and pill count. J Dev Behav Pediatr 2008; 29: 377-384
• 35 Feiterna-Sperling C, Edelmann A, Nickel R et al. Pandemic Influenza A (H1N1) Outbreak in 15 School-Aged HIV-Infected Children. Klin Padiatr 2010; 222
• 36 Feldmann . Evidence-based Pediatrics. BC Decker, Hamilton; 1st edition 2000. DOI:
• 37 Fisac C, Fumero E, Crespo M et al. Metabolic benefits 24 months after replacing a protease inhibitor with abacavir, efavirenz or nevirapine. AIDS 2005; 19: 917-925
• 38 Funk MB, Notheis G, Schuster T et al. Effect of first line therapy including efavirenz and two nucleoside reverse transcriptase inhibitors in HIV-infected children. Eur J Med Res 2005; 10: 503-508
• 39 Gafni RI, Hazra R, Reynolds JC et al. Tenofovir disoproxil fumarate and an optimized background regimen of antiretroviral agents as salvage therapy: impact on bone mineral density in HIV-infected children. Pediatrics 2006; 118: e711-e718
• 40 Galli L, de Martino M, Tovo PA et al. Predictive value of the HIV paediatric classification system for the long-term course of perinatally infected children. Int J Epidemiol 2000; 29: 573-578
• 41 Gathe Jr JC, Ive P, Wood R et al. SOLO: 48-week efficacy and safety comparison of once-daily fosamprenavir/ritonavir versus twice-daily nelfinavir in naive HIV-1-infected patients. AIDS 2004; 18: 1529-1537
• 42 Gaughan DM, Mofenson LM, Hughes MD et al. Osteonecrosis of the hip (Legg-Calve-Perthes disease) in human immunodeficiency virus-infected children. Pediatrics 2002; 109: E74
• 43 Ghosh S, Neubert J, Niehues T et al. Induction Maintenance Concept for HAART as Initial Treatment in HIV Infected Infants. Eur J Med REs 2011; 16: 234-288
• 44 Giacomet V, Albano F, Starace F et al. Adherence to antiretroviral therapy and its determinants in children with human immunodeficiency virus infection: a multicentre, national study. Acta Paediatr 2003; 92: 1398-1402
• 45 Giaquinto C, Morelli E, Fregonese F et al. Current and future antiretroviral treatment options in paediatric HIV infection. Clin Drug Investig 2008; 28: 375-397
• 46 Goetghebuer T, Haelterman E, Le Chenadec J et al. Effect of early antiretroviral therapy on the risk of AIDS/death in HIV-infected infants. AIDS 2009; 23: 597-604
• 47 Green H, Gibb DM, Compagnucci A et al. A randomized controlled trial of genotypic HIV drug resistance testing in HIV-1-infected children: the PERA (PENTA 8) trial. Antivir Ther 2006; 11: 857-867
• 48 Green H, Gibb DM, Walker AS et al. Lamivudine/abacavir maintains virological superiority over zidovudine/lamivudine and zidovudine/abacavir beyond 5 years in children. AIDS 2007; 21: 947-955
• 49 Group HPPMCS . Predictive value of absolute CD4 cell count for disease progression in untreated HIV-1-infected children. AIDS 2006; 20: 1289-1294
• 50 Gupta RK, Gibb DM, Pillay D. Management of paediatric HIV-1 resistance. Curr Opin Infect Dis 2009; 22: 256-263
• 51 Hunt GM, Coovadia A, Abrams EJ et al. HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine. AIDS 2011; DOI: 10.1097/QAD.0b013e3283492180.
• 52 Imaz A, del Saz SV, Ribas MA et al. Raltegravir, etravirine, and ritonavir-boosted darunavir: a safe and successful rescue regimen for multidrug-resistant HIV-1 infection. J Acquir Immune Defic Syndr 2009; 52: 382-386
• 53 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
• 54 Kiser JJ, Rutstein RM, Samson P et al. Atazanavir and Atazanavir/Ritonavir Pharmacokinetics in HIV-Infected Infants, Children, and Adolescents. AIDS 2011; DOI: 10.1097/QAD.0b013e328348fc41.
• 55 Kline MW, Blanchard S, Fletcher CV et al. A phase I study of abacavir (1592U89) alone and in combination with other antiretroviral agents in infants and children with human immunodeficiency virus infection. AIDS Clinical Trials Group 330 Team. Pediatrics 1999; 103: e47
• 56 Kredo T, Van der Walt JS, Siegfried N et al. Therapeutic drug monitoring of antiretrovirals for people with HIV. Cochrane Database Syst Rev 2009; DOI: 10.1002/14651858.CD007268.pub2:. CD007268
• 57 Lainka E, Oezbek S, Falck M et al. Marked dyslipidemia in human immunodeficiency virus-infected children on protease inhibitor-containing antiretroviral therapy. Pediatrics 2002; 110: e56
• 58 Lalezari JP, Henry K, O’Hearn M et al. Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America. N Engl J Med 2003; 348: 2175-2185
• 59 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
• 60 Lazzarin A, Clotet B, Cooper D et al. Efficacy of enfuvirtide in patients infected with drug-resistant HIV-1 in Europe and Australia. N Engl J Med 2003; 348: 2186-2195
• 61 Lima VD, Harrigan R, Bangsberg DR et al. The combined effect of modern highly active antiretroviral therapy regimens and adherence on mortality over time. J Acquir Immune Defic Syndr 2009; 50: 529-536
• 62 Lockman S, Shapiro RL, Smeaton LM et al. Response to antiretroviral therapy after a single, peripartum dose of nevirapine. N Engl J Med 2007; 356: 135-147
• 63 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: 1343-1349
• 64 Luzuriaga K, Bryson Y, McSherry G et al. Pharmacokinetics, safety, and activity of nevirapine in human immunodeficiency virus type 1-infected children. J Infect Dis 1996; 174: 713-721
• 65 Luzuriaga K, McManus M, Mofenson L et al. A trial of three antiretroviral regimens in HIV-1-infected children. N Engl J Med 2004; 350: 2471-2480
• 66 Makinson A, Reynes J. The fusion inhibitor enfuvirtide in recent antiretroviral strategies. Curr Opin HIV AIDS 2009; 4: 150-158
• 67 Mallal S, Phillips E, Carosi G et al. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med 2008; 358: 568-579
• 68 McComsey G, Bhumbra N, Ma JF et al. Impact of protease inhibitor substitution with efavirenz in HIV-infected children: results of the First Pediatric Switch Study. Pediatrics 2003; 111: e275-e281
• 69 McCrindle BW, Urbina EM, Dennison BA et al. Drug therapy of high-risk lipid abnormalities in children and adolescents: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee, Council of Cardiovascular Disease in the Young, with the Council on Cardiovascular Nursing. Circulation 2007; 115: 1948-1967
• 70 McKeage K, Scott LJ. Darunavir: in treatment-experienced pediatric patients with HIV-1 infection. Paediatr Drugs 2010; 12: 123-131
• 71 Menson EN, Walker AS, Sharland M et al. Underdosing of antiretrovirals in UK and Irish children with HIV as an example of problems in prescribing medicines to children, 1997–2005: cohort study. BMJ 2006; 332: 1183-1187
• 72 Meynard JL, Vray M, Morand-Joubert L et al. Phenotypic or genotypic resistance testing for choosing antiretroviral therapy after treatment failure: a randomized trial. AIDS 2002; 16: 727-736
• 73 Miller V, Sabin C, Hertogs K et al. Virological and immunological effects of treatment interruptions in HIV-1 infected patients with treatment failure. AIDS 2000; 14: 2857-2867
• 74 Mofenson LM, Korelitz J, Meyer 3rd 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
• 75 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
• 76 Neely MN, Rakhmanina NY. Pharmacokinetic optimization of antiretroviral therapy in children and adolescents. Clin Pharmacokinet 2011; 50: 143-189
• 77 Niehues T, Baumann U, Buchholz B et al. Empfehlungen zur antiretroviralen Therapie bei HIV-infizierten Kindern 2006 – Vollständig überarbeitetes und aktualisiertes Konsensus-Statement der Pädiatrischen Arbeitsgemeinschaft AIDS (PAAD) und der Deutschen Gesellschaft für Pädiatrische Infektiologie (DGPI). Monatsschr Kinderheilkd 2006; 154 (06) 563-573
• 78 Niehues T, Wintergerst U, Funk M et al. Empfehlungen zur antiretroviralen Therapie bei HIV-infizierten Kindern – Vollständig überarbeitetes und aktualisiertes Konsensus-Statement der Pädiatrischen Arbeitsgemeinschaft AIDS (PAAD) und der Deutschen Gesellschaft für Pädiatrische Infektiologie (DGPI) 2001; Monatsschr Kinderheilkd 2001; 12 () 1372-1382
• 79 Noguera A, Fortuny C, Munoz-Almagro C et al. Hyperlactatemia in human immunodeficiency virus-uninfected infants who are exposed to antiretrovirals. Pediatrics 2004; 114: e598-e603
• 80 Noguera A, Fortuny C, Sanchez E et al. Hyperlactatemia in human immunodeficiency virus-infected children receiving antiretroviral treatment. Pediatr Infect Dis J 2003; 22: 778-782
• 81 Nso Roca AP, Larru B, Bellon JM et al. HIV-infected adolescents: relationship between atazanavir plasma levels and bilirubin concentrations. J Adolesc Health 2011; 48: 100-102
• 82 Palladino C, Briz V, Gonzalez-Tome MI et al. Short communication: evaluation of the effect of enfuvirtide in 11 HIV-1 vertically infected pediatric patients outside clinical trials. AIDS Res Hum Retroviruses 2010; 26: 301-305
• 83 Palladino C, Briz V, Policarpo SN et al. Long-term efficacy and safety of fosamprenavir in human immunodeficiency virus-infected pediatric patients. Pediatr Infect Dis J 2010; 29: 563-566
• 84 Palumbo P, Lindsey JC, Hughes MD et al. Antiretroviral treatment for children with peripartum nevirapine exposure. N Engl J Med 2010; 363: 1510-1520
• 85 Palumbo PE, Raskino C, Fiscus S et al. Predictive value of quantitative plasma HIV RNA and CD4+ lymphocyte count in HIV-infected infants and children. JAMA 1998; 279: 756-761
• 86 Paterson DL, Swindells S, Mohr J et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med 2000; 133: 21-30
• 87 Persaud D, Zhou Y, Siliciano JM et al. Latency in human immunodeficiency virus type 1 infection: no easy answers. J Virol 2003; 77: 1659-1665
• 88 Reddington C, Cohen J, Baldillo A et al. Adherence to medication regimens among children with human immunodeficiency virus infection. Pediatr Infect Dis J 2000; 19: 1148-1153
• 89 Resino S, Larru B, Maria Bellon J et al. Effects of highly active antiretroviral therapy with nelfinavir in vertically HIV-1 infected children: 3 years of follow-up. Long-term response to nelfinavir in children. BMC Infect Dis 2006; 6: 107
• 90 Sabin CA, Worm SW, Weber R et al. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration. Lancet 2008; 371: 1417-1426
• 91 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
• 92 Salazar JC, Cahn P, Yogev R et al. Efficacy, safety and tolerability of tipranavir coadministered with ritonavir in HIV-1-infected children and adolescents. AIDS 2008; 22: 1789-1798
• 93 Sax PE, Tierney C, Collier AC et al. Abacavir-lamivudine versus tenofovir-emtricitabine for initial HIV-1 therapy. N Engl J Med 2009; 361: 2230-2240
• 94 Schieferstein CBT. Management von Nebenwirkungen HIV Buch 2011;
• 95 Simoni JM, Montgomery A, Martin E et al. Adherence to antiretroviral therapy for pediatric HIV infection: a qualitative systematic review with recommendations for research and clinical management. Pediatrics 2007; 119: e1371-e1383
• 96 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
• 97 Steigbigel RT, Cooper DA, Teppler H et al. Long-term efficacy and safety of Raltegravir combined with optimized background therapy in treatment-experienced patients with drug-resistant HIV infection: week 96 results of the BENCHMRK 1 and 2 Phase III trials. Clin Infect Dis 2010; 50: 605-612
• 98 Study TEC . Natural history of vertically acquired human immunodeficiency virus-1 infection. The European Collaborative Study. Pediatrics 1994; 94: 815-819
• 99 Tebas P, Powderly WG, Claxton S et al. Accelerated bone mineral loss in HIV-infected patients receiving potent antiretroviral therapy. AIDS 2000; 14: F63-F67
• 100 Teglas JP, Quartier P, Treluyer JM et al. Tolerance of efavirenz in children. AIDS 2001; 15: 241-243
• 101 Tudor-Williams . Baby Cocktail! A protease-sparing 4 drug combination for symptomatic infants. XIV International AIDS Conference Barcelona, Spain 2002; DOI: . July 7–12, Abstract MoOrB1129
• 102 Tural C, Ruiz L, Holtzer C et al. Clinical utility of HIV-1 genotyping and expert advice: the Havana trial. AIDS 2002; 16: 209-218
• 103 Turner D, Brenner BG, Routy JP et al. Rationale for maintenance of the M184v resistance mutation in human immunodeficiency virus type 1 reverse transcriptase in treatment experienced patients. New Microbiol 2004; 27: 31-39
• 104 Van Dyke RB, Lee S, Johnson GM et al. Reported adherence as a determinant of response to highly active antiretroviral therapy in children who have human immunodeficiency virus infection. Pediatrics 2002; 109: e61
• 105 Van Dyke RB, Wang L, Williams PL. Toxicities associated with dual nucleoside reverse-transcriptase inhibitor regimens in HIV-infected children. J Infect Dis 2008; 198: 1599-1608
• 106 Van Rompay KK, Matthews TB, Higgins J et al. Virulence and reduced fitness of simian immunodeficiency virus with the M184V mutation in reverse transcriptase. J Virol 2002; 76: 6083-6092
• 107 van Rossum AM, Fraaij PL, de Groot R. Efficacy of highly active antiretroviral therapy in HIV-1 infected children. Lancet Infect Dis 2002; 2: 93-102
• 108 Verweel G, Sharland M, Lyall H et al. Nevirapine use in HIV-1-infected children. AIDS 2003; 17: 1639-1647
• 109 Vigano A, Giacomet V. Nucleoside analogues toxicities related to mitochondrial dysfunction: focus on HIV-infected children. Antivir Ther 2005; 10: M53-M64
• 110 Vigano A, Zuccotti GV, Puzzovio M et al. Tenofovir disoproxil fumarate and bone mineral density: a 60-month longitudinal study in a cohort of HIV-infected youths. Antivir Ther 2010; 15: 1053-1058
• 111 Violari A, Cotton MF, Gibb DM et al. Early antiretroviral therapy and mortality among HIV-infected infants. N Engl J Med 2008; 359: 2233-2244
• 112 Vray M, Meynard JL, Dalban C et al. Predictors of the virological response to a change in the antiretroviral treatment regimen in HIV-1-infected patients enrolled in a randomized trial comparing genotyping, phenotyping and standard of care (Narval trial, ANRS 088). Antivir Ther 2003; 8: 427-434
• 113 Vreeman RC, Wiehe SE, Pearce EC et al. A systematic review of pediatric adherence to antiretroviral therapy in low- and middle-income countries. Pediatr Infect Dis J 2008; 27: 686-691
• 114 Wahn V, Bialek R, Böhler T. Empfehlungen zur antiretroviralen Therapie bei HIV-infizierten Kindern. Monatsschr Kinderheilkd 1998; 146: 1081-1091
• 115 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
• 116 Watson DC, Farley JJ. Efficacy of and adherence to highly active antiretroviral therapy in children infected with human immunodeficiency virus type 1. Pediatr Infect Dis J 1999; 18: 682-689
• 117 Wegner SA, Wallace MR, Aronson NE et al. Long-term efficacy of routine access to antiretroviral-resistance testing in HIV type 1-infected patients: results of the clinical efficacy of resistance testing trial. Clin Infect Dis 2004; 38: 723-730
• 118 Wintergerst U, Hoffmann F, Jansson A et al. Antiviral efficacy, tolerability and pharmacokinetics of efavirenz in an unselected cohort of HIV-infected children. J Antimicrob Chemother 2008; 61: 1336-1339
• 119 Yazdanpanah Y, Fagard C, Descamps D et al. High rate of virologic suppression with raltegravir plus etravirine and darunavir/ritonavir among treatment-experienced patients infected with multidrug-resistant HIV: results of the ANRS 139 TRIO trial. Clin Infect Dis 2009; 49: 1441-1449
• 120 Zuccotti G, Vigano A, Gabiano C et al. Antiretroviral therapy and bone mineral measurements in HIV-infected youths. Bone 2010; 46: 1633-1638