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Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for the use of antiretroviral agents in pediatric HIV infection. Available at http://aidsinfo.nih.gov/OrderPublication/ OrderPubsBrowseSearchResultsTable.aspx?MenuItem=AIDSinfoTools&ID=115. [Accessed 12 January 2008]
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Collaborative HIV Paediatric Study Steering Committee. Underdosing of antiretrovirals in UK and Irish children with HIV as an example of problems in prescribing medicines to children, 1997-2005: Cohort study
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Menson EN, Walker AS, Sharland M, et al., Collaborative HIV Paediatric Study Steering Committee. 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.
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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.
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Collaboration of Observational HIV Epidemiological Research Europe (COHERE) Study Group. Response to combination antiretroviral therapy: variation by age. AIDS 2008; 22:1463-1473. This paper importantly showed that children do not respond as well as adults to first-line HAART.
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Collaboration of Observational HIV Epidemiological Research Europe (COHERE) Study Group. Response to combination antiretroviral therapy: variation by age. AIDS 2008; 22:1463-1473. This paper importantly showed that children do not respond as well as adults to first-line HAART.
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14
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Efficacy of highly active antiretroviral therapy in HIV-infected children participating in Thailand's National Access to Antiretroviral Program
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Puthanakit T, Oberdorfer A, Akarathum N, et al. Efficacy of highly active antiretroviral therapy in HIV-infected children participating in Thailand's National Access to Antiretroviral Program. Clin Infect Dis 2005; 41:100-107.
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Adjé-Touré C, Hanson DL, Talla-Nzussouo N, et al. Virologic and immunologic response to antiretroviral therapy and predictors of HIV type 1 drug resistance in children receiving treatment in Abidjan, Côte d'Ivoire. AIDS Res Hum Retroviruses 2008; 24:911-917. This work provided data on resistance following first-line failure in a setting without regular viral load monitoring.
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Adjé-Touré C, Hanson DL, Talla-Nzussouo N, et al. Virologic and immunologic response to antiretroviral therapy and predictors of HIV type 1 drug resistance in children receiving treatment in Abidjan, Côte d'Ivoire. AIDS Res Hum Retroviruses 2008; 24:911-917. This work provided data on resistance following first-line failure in a setting without regular viral load monitoring.
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16
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Chaix ML, Rouet F, Kouakoussui KA, et al. Genotypic human immunodeficiency virus type 1 drug resistance in highly active antiretroviral therapy-treated children in Abidjan, Côte d'Ivoire. Pediatr Infect Dis J 2005; 24:1072-1076.
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Pillay V, Pillay C, Kantor R, et al. HIV type 1 subtype C drug resistance among pediatric and adult South African patients failing antiretroviral therapy. AIDS Res Hum Retroviruses 2008; 24:1449-1454.
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Effectiveness of highly active antiretroviral therapy in HIV-positive children: Evaluation at 12 months in a routine program in Cambodia
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This study provided valuable resistance data on children aged more than 13 years using generic adult stavudine/lamivudine and nevirapine
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Janssens B, Raleigh B, Soeung S, et al. Effectiveness of highly active antiretroviral therapy in HIV-positive children: evaluation at 12 months in a routine program in Cambodia. Pediatrics 2007; 120:e1134-e1140. This study provided valuable resistance data on children aged more than 13 years using generic adult stavudine/lamivudine and nevirapine.
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Pediatrics
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Janssens, B.1
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19
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High prevalence of antiretroviral drug resistance mutations and HIV-1 non-B subtype strains from children receiving antiretroviral therapy regimen according to the 2006 revised WHO recommendations
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This study demonstrated low virological response rates and high rates of resistance at only 6 months following initiation of HAART
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Gody J-C, Charpentier C, Mbitikon O, Si-Mohamed A. High prevalence of antiretroviral drug resistance mutations and HIV-1 non-B subtype strains from children receiving antiretroviral therapy regimen according to the 2006 revised WHO recommendations. J Acquir Immune Defic Syndr 2008; 49:566-569. This study demonstrated low virological response rates and high rates of resistance at only 6 months following initiation of HAART.
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Sungkanuparph S, Manosuthi W, Kiertiburanakul S, et al. Options for a second-line antiretroviral regimen for HIV type 1-infected patients whose initial regimen of a fixed-dose combination of stavudine, lamivudine, and nevirapine fails. Clin Infect Dis 2007; 44:447-452.
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South Africa Resistance Cohort Study Team. Prevalence of HIV-1 drug resistance after failure of a first highly active antiretroviral therapy regimen in KwaZulu Natal, South Africa
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This paper, although looking at adults, reported resistance data on a large number of patients in a resource-poor setting
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Marconi VC, Sunpath H, Lu Z, et al., South Africa Resistance Cohort Study Team. Prevalence of HIV-1 drug resistance after failure of a first highly active antiretroviral therapy regimen in KwaZulu Natal, South Africa. Clin Infect Dis 2008; 46:1589-1597. This paper, although looking at adults, reported resistance data on a large number of patients in a resource-poor setting.
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Clin Infect Dis
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Marconi, V.C.1
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Parikh UM, Bacheler L, Koontz D, Mellors JW. The K65R mutation in human immunodeficiency virus type 1 reverse transcriptase exhibits bidirectional phenotypic antagonism with thymidine analog mutations. J Virol 2006; 80:4971-4977.
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Macassa E, Delaugerre C, Teglas JP, et al. Change to a once-daily combination including boosted atazanavir in HIV-1-infected children. Pediatr Infect Dis J 2006; 25:809-814.
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Mullen J, Leech S, O'Shea S, et al. Antiretroviral drug resistance among HIV-1 infected children failing treatment. J Med Virol 2002; 68:299-304.
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25
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Pediatric AIDS Clinical Trials Group 381 Study Team. Analyses of HIV-1 drug-resistance profiles among infected adolescents experiencing delayed antiretroviral treatment switch after initial nonsuppressive highly active antiretroviral therapy
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This study highlights the resistance implications associated with delayed switch after viral failure in adolescents
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Agwu A, Lindsey JC, Ferguson K, et al., Pediatric AIDS Clinical Trials Group 381 Study Team. Analyses of HIV-1 drug-resistance profiles among infected adolescents experiencing delayed antiretroviral treatment switch after initial nonsuppressive highly active antiretroviral therapy. AIDS Patient Care STDS 2008; 22:545-552. This study highlights the resistance implications associated with delayed switch after viral failure in adolescents.
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Agwu, A.1
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Bartlett JA, Buda JJ, von Scheele B, et al. Minimizing resistance consequences after virologic failure on initial combination therapy: a systematic overview. J Acquir Immune Defic Syndr 2006; 41:323-331.
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Gupta R, Hill A, Sawyer AW, Pillay D. Emergence of drug resistance in HIV type 1-infected patients after receipt of first-line highly active antiretroviral therapy: a systematic review of clinical trials. Clin Infect Dis 2008; 47:712-722. This meta-analysis using data from 8000 patients compares resistance outcomes following boosted protease inhibitor vs NNRTI-based HAART, showing that resistance to both the third agent and NRTI is lower when boosted protease inhibitor are used.
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28
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Sáez-Llorens X, Violari A, Deetz CO, et al. Forty-eight-week evaluation of lopinavir/ritonavir, a new protease inhibitor, in human immunodeficiency virusinfected children. Pediatr Infect Dis J 2003; 22:216-224.
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Delaugerre C, Teglas JP, Treluyer JM, et al. Predictive factors of virologic success in HIV-1-infected children treated with lopinavir/ritonavir. J Acquir Immune Defic Syndr 2004; 37:1269-1275.
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Pediatric AIDS Clinical Trials Group P1030 Team. Early archiving and predominance of nonnucleoside reverse transcriptase inhibitor-resistant HIV-1 among recently infected infants born in the United States
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Persaud D, Palumbo P, Ziemniak C, et al., Pediatric AIDS Clinical Trials Group P1030 Team. Early archiving and predominance of nonnucleoside reverse transcriptase inhibitor-resistant HIV-1 among recently infected infants born in the United States. J Infect Dis 2007; 195:1402-1410.
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AIDS Clinical Trials Group Study A5142 Team. Class-sparing regimens for initial treatment of HIV-1 infection
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This randomized trial showed that NNRTI-based and protease inhibitor based regimens were highly efficacious; although viral failure was more common in patients using boosted protease inhibitor, prevalence of resistance was lower in this group
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Riddler SA, Haubrich R, DiRienzo AG, et al., AIDS Clinical Trials Group Study A5142 Team. Class-sparing regimens for initial treatment of HIV-1 infection. N Engl J Med 2008; 358:2095-2106. This randomized trial showed that NNRTI-based and protease inhibitor based regimens were highly efficacious; although viral failure was more common in patients using boosted protease inhibitor, prevalence of resistance was lower in this group.
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N Engl J Med
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Riddler, S.A.1
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Resino S, Bellon JM, Ramos JT, et al. Salvage lopinavir-ritonavir therapy in human immunodeficiency virus-infected children. Pediatr Infect Dis J 2004; 23:923-930.
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Ramos JT, De Jose MI, Duenas J, et al. Safety and antiviral response at 12 months of lopinavir/ritonavir therapy in human immunodeficiency virus-1-infected children experienced with three classes of antiretrovirals. Pediatr Infect Dis J 2005; 24:867-873.
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Ramos, J.T.1
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Gibb DM, Walker AS, Kaye S, et al. Evolution of antiretroviral phenotypic and genotypic drug resistance in antiretroviral-naive HIV-1-infected children treated with abacavir/lamivudine, zidovudine/lamivudine or abacavir/zidovudine, with or without nelfinavir (the PENTA 5 trial). Antivir Ther 2002; 7:293-303.
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Gibb, D.M.1
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Impact of human immunodeficiency virus type 1 subtypes on virologic response and emergence of drug resistance among children in the Paediatric European Network for Treatment of AIDS (PENTA) 5 trial
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Pillay D, Walker AS, Gibb DM, et al. Impact of human immunodeficiency virus type 1 subtypes on virologic response and emergence of drug resistance among children in the Paediatric European Network for Treatment of AIDS (PENTA) 5 trial. J Infect Dis 2002; 186:617-625.
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Pillay, D.1
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36
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59949103751
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PACTG 1051/BI Study Team. Efficacy, safety and tolerability of tipranavir coadministered with ritonavir in HIV-1-infected children and adolescents
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An important study using the second-generation protease inhibitor tipranavir in children
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Salazar JC, Cahn P, Yogev R, et al., PACTG 1051/BI Study Team. Efficacy, safety and tolerability of tipranavir coadministered with ritonavir in HIV-1-infected children and adolescents. AIDS 2008; 22:1789-1798. An important study using the second-generation protease inhibitor tipranavir in children.
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AIDS
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Salazar, J.C.1
Cahn, P.2
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Baxter JD, Schapiro JM, Boucher CA, et al. Genotypic changes in human immunodeficiency virus type 1 protease associated with reduced susceptibility and virologic response to the protease inhibitor tipranavir. J Virol 2006; 80:10794-10801.
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Blanche S, Bologna R, Cahn P, et al. 48-week safety and efficacy of darunavir/ritonavir in treatment-experienced children and adolescents in DELPHI. Proceedings of the 48th Interscience Conference on Antimicrobial Agents and Chemotherapy; 25-28 October 2008; Washington: American Society of Microbiology; abstract H-894. An important salvage study using the second-generation protease inhibitor darunavir in children.
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Blanche S, Bologna R, Cahn P, et al. 48-week safety and efficacy of darunavir/ritonavir in treatment-experienced children and adolescents in DELPHI. Proceedings of the 48th Interscience Conference on Antimicrobial Agents and Chemotherapy; 25-28 October 2008; Washington: American Society of Microbiology; abstract H-894. An important salvage study using the second-generation protease inhibitor darunavir in children.
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39
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HIV-NAT017 Study Team. Double boosted protease inhibitors, saquinavir, and lopinavir/ritonavir, in nucleoside pretreated children at 48 weeks
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An interesting study into double boosted protease inhibitor in children
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Kosalaraksa P, Bunupuradah T, Engchanil C, et al., HIV-NAT017 Study Team. Double boosted protease inhibitors, saquinavir, and lopinavir/ritonavir, in nucleoside pretreated children at 48 weeks. Pediatr Infect Dis J 2008; 27:623-628. An interesting study into double boosted protease inhibitor in children.
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Kosalaraksa, P.1
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PACTG 1038 Team. Pharmacokinetics of high-dose lopinavir-ritonavir with and without saquinavir or nonnucleoside reverse transcriptase inhibitors in human immunodeficiency virus-infected pediatric and adolescent patients previously treated with protease inhibitors
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Important pharmacokinetic data for LPV as part of a single or dual boosted protease inhibitor strategy
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Robbins BL, Capparelli EV, Chadwick EG, et al., PACTG 1038 Team. Pharmacokinetics of high-dose lopinavir-ritonavir with and without saquinavir or nonnucleoside reverse transcriptase inhibitors in human immunodeficiency virus-infected pediatric and adolescent patients previously treated with protease inhibitors. Antimicrob Agents Chemother 2008; 52:3276-3283. Important pharmacokinetic data for LPV as part of a single or dual boosted protease inhibitor strategy.
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Robbins, B.L.1
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Chadwick, E.G.3
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Important data on transmitted resistance in the Indian subcontinent
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Ghent Group on HIV in Women and Children. Prevalence of resistance to nevirapine in mothers and children after single-dose exposure to prevent vertical transmission of HIV-1: A metaanalysis
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A very important meta-analysis of studies into PMTCT with single-dose NVP vs NVP combined with one or more NRTI
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Arrivé E, Newell ML, Ekouevi DK, et al., Ghent Group on HIV in Women and Children. Prevalence of resistance to nevirapine in mothers and children after single-dose exposure to prevent vertical transmission of HIV-1: a metaanalysis. Int J Epidemiol 2007; 36:1009-1021. A very important meta-analysis of studies into PMTCT with single-dose NVP vs NVP combined with one or more NRTI.
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Six Week Extended-Dose Nevirapine (SWEN) Study Team, Bedri A, Gudetta B, et al. Extended-dose nevirapine to 6 weeks of age for infants to prevent HIV transmission via breastfeeding in Ethiopia, India, and Uganda: an analysis of three randomised controlled trials. Lancet 2008; 372:300-313. This study showed that extended prophylaxis substantially reduced transmission associated with breast-feeding in subtype A, C and D infected patients.
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Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission
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This study demonstrates that extended NVP prophylaxis in infants is associated with increased NVP resistance in those who become infected
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Church JD, Omer SB, Guay LA, et al. Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission. J Infect Dis 2008; 198:1075-1082. This study demonstrates that extended NVP prophylaxis in infants is associated with increased NVP resistance in those who become infected.
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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. This very important trial of early vs deferred HAART in infants showed a mortality benefit for the former group. WHO guidelines were changed as a result of this study.
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