title: Long-Term Changes of Subcutaneous Fat Mass in HIV-Infected Children on Antiretroviral Therapy: A Retrospective Analysis of Longitudinal Data from Two Pediatric HIV-Cohorts.
abstract: OBJECTIVE
  Longitudinal studies objectively evaluating changes in regional fat distribution of HIV-infected children assessed by whole body dual energy X-ray absorptiometry (DEXA) are scarce, whilst this long-term effect of HIV and antiretroviral therapy (cART) is an important issue in infected children in need for lifelong treatment.
  
  
  METHODS
  We assessed regional fat distribution over time, measured with sequential DEXA-scans in HIV-infected children on cART in cohorts from South Africa (SA) and the Netherlands (NL), and in healthy controls (SA). Limb and trunk fat Z-scores were calculated with the lambda-mu-sigma (LMS) method. Multivariable linear regression models with mixed effects were used to investigate the effect of cART compounds on body fat distribution over time.
  
  
  RESULTS
  In total, 218 children underwent 445 DEXA assessments with a median follow-up of 3.5 years. Fat mass in all limbs was decreased in HIV-infected children compared to controls (arm fat Z-score: coefficient -0.4813; P = 0.006, leg fat Z-score: coefficient -0.4345; P = 0.013). In the HIV-infected group, stavudine treatment was associated with lower subcutaneous fat mass (arm fat Z-score: coefficient -0.5838; P = 0.001), with an additional cumulative exposure effect (arm fat Z-score: coefficient -0.0867; P = 0.003).
  
  
  CONCLUSIONS
  Our study shows that subcutaneous fat loss is still prevalent in HIV-infected children on cART, and is strongly associated with cumulative stavudine exposure. These results underline the need for early detection of subcutaneous fat loss and alternative treatment options for HIV-infected children globally.
authors.affiliation: Department of Paediatric Haematology, Immunology, and Infectious Diseases, Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Sophie
authors.initials: S
authors.lastname: Cohen
authors.affiliation: KID-CRU (Children's Infectious Diseases Clinical Research Unit), Tygerberg Children's Hospital and Stellenbosch University, Cape Town, South Africa.
authors.forename: Steve
authors.initials: S
authors.lastname: Innes
authors.affiliation: Department of Paediatrics, Wilhelmina Children's Hospital, University Medical Centre Utrecht, University of Utrecht, Utrecht, The Netherlands.
authors.forename: Sibyl P M
authors.initials: SP
authors.lastname: Geelen
authors.affiliation: Childhood Nutrition Research Centre, University College London, Institute of Child Health, London, United Kingdom.
authors.forename: Jonathan C K
authors.initials: JC
authors.lastname: Wells
authors.affiliation: Stichting HIV Monitoring, Amsterdam, The Netherlands.
authors.forename: Colette
authors.initials: C
authors.lastname: Smit
authors.affiliation: Department of Paediatrics, Wilhelmina Children's Hospital, University Medical Centre Utrecht, University of Utrecht, Utrecht, The Netherlands.
authors.forename: Tom F W
authors.initials: TF
authors.lastname: Wolfs
authors.affiliation: Department of Nuclear Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Berthe L F
authors.initials: BL
authors.lastname: van Eck-Smit
authors.affiliation: Department of Paediatric Haematology, Immunology, and Infectious Diseases, Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Taco W
authors.initials: TW
authors.lastname: Kuijpers
authors.affiliation: Stichting HIV Monitoring, Amsterdam, The Netherlands; Department of Global Health and Amsterdam Institute of Global Health and Development, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.affiliation: Department of Paediatric Haematology, Immunology, and Infectious Diseases, Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Henriette J
authors.initials: HJ
authors.lastname: Scherpbier
authors.affiliation: Department of Paediatric Haematology, Immunology, and Infectious Diseases, Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Dasja
authors.initials: D
authors.lastname: Pajkrt
authors.affiliation: Department of Paediatric Haematology, Immunology, and Infectious Diseases, Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Madeleine J
authors.initials: MJ
authors.lastname: Bunders
mesh_terms: D015502:Absorptiometry, Photon; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009426:Netherlands; D012189:Retrospective Studies; D050151:Subcutaneous Fat / Q000000981:diagnostic imaging*
chemical_list: D019380:Anti-HIV Agents