title: Sequencing paediatric antiretroviral therapy in the context of a public health approach.
abstract: BACKGROUND
  As access to prevention of mother-to-child transmission (PMTCT) efforts has increased, the total number of children being born with HIV has significantly decreased. However, those children who do become infected after PMTCT failure are at particular risk of HIV drug resistance, selected by exposure to maternal or paediatric antiretroviral drugs used before, during or after birth. As a consequence, the response to antiretroviral therapy (ART) in these children may be compromised, particularly when non-nucleoside reverse transcriptase inhibitors (NNRTIs) are used as part of the first-line regimen. We review evidence guiding choices of first- and second-line ART.
  
  
  CONCLUSIONS
  Children generally respond relatively well to ART. Clinical trials show the superiority of protease inhibitor (PI)- over NNRTI-based treatment in young children, but observational reports of NNRTI-containing regimens are usually favourable as well. This is reassuring as national guidelines often still recommend the use of NNRTI-based treatment for PMTCT-unexposed young children, due to the higher costs of PIs. After failure of NNRTI-based, first-line treatment, the rate of acquired drug resistance is high, but HIV may well be suppressed by PIs in second-line ART. By contrast, there are currently no adequate alternatives in resource-limited settings (RLS) for children failing either first- or second-line, PI-containing regimens.
  
  
  CONCLUSIONS
  Affordable salvage treatment options for children in RLS are urgently needed.
authors.affiliation: Amsterdam Institute for Global Health and Development and Department of Global Health, Academic Medical Center of the University of Amsterdam, The Netherlands.|Global Child Health Group, Emma Children's Hospital/Academic Medical Center of the University of Amsterdam, The Netherlands; r.boerma@aighd.org.
authors.forename: Ragna S
authors.initials: RS
authors.lastname: Boerma
authors.affiliation: Amsterdam Institute for Global Health and Development and Department of Global Health, Academic Medical Center of the University of Amsterdam, The Netherlands.
authors.forename: T Sonia
authors.initials: TS
authors.lastname: Boender
authors.affiliation: Global Child Health Group, Emma Children's Hospital/Academic Medical Center of the University of Amsterdam, The Netherlands.
authors.forename: Michael Boele
authors.initials: MB
authors.lastname: van Hensbroek
authors.affiliation: Amsterdam Institute for Global Health and Development and Department of Global Health, Academic Medical Center of the University of Amsterdam, The Netherlands.
authors.forename: Tobias F
authors.initials: TF
authors.lastname: Rinke de Wit
authors.affiliation: Amsterdam Institute for Global Health and Development and Department of Global Health, Academic Medical Center of the University of Amsterdam, The Netherlands.|Division of Infectious Diseases, Department of Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Kim C E
authors.initials: KC
authors.lastname: Sigaloff
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D002648:Child; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D011634:Public Health; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors
keywords: HIV drug resistance; antiretroviral therapy; low- and middle-income countries; non-nucleoside reverse transcriptase inhibitor; paediatric HIV; protease inhibitor