title: High prevalence of lipoatrophy in pre-pubertal South African children on antiretroviral therapy: a cross-sectional study.
abstract: BACKGROUND
  Despite changes in WHO guidelines, stavudine is still used extensively for treatment of pediatric HIV in the developing world. Lipoatrophy in sub-Saharan African children can be stigmatizing and have far-reaching consequences. The severity and extent of lipoatrophy in pre-pubertal children living in sub-Saharan Africa is unknown.
  
  
  METHODS
  In this cross-sectional study, children who were 3-12 years old, on antiretroviral therapy and pre-pubertal were recruited from a Family HIV Clinic in South Africa. Lipoatrophy was identified and graded by consensus between two HIV pediatricians using a standardized grading scale. A professional dietician performed formal dietary assessment and anthropometric measurements of trunk and limb fat. Previous antiretroviral exposures were recorded. In a Dual-Energy X-ray Absorbtiometry (DXA) substudy body composition was determined in 42 participants.
  
  
  RESULTS
  Among 100 recruits, the prevalence of visually obvious lipoatrophy was 36% (95% CI: 27%-45%). Anthropometry and DXA measurements corroborated the clinical diagnosis of lipoatrophy: Both confirmed significant, substantial extremity fat loss in children with visually obvious lipoatrophy, when adjusted for age and sex. Adjusted odds ratio for developing lipoatrophy was 1.9 (95% CI: 1.3 - 2.9) for each additional year of accumulated exposure to standard dose stavudine. Cumulative time on standard dose stavudine was significantly associated with reductions in biceps and triceps skin-fold thickness (p=0.008).
  
  
  CONCLUSIONS
  The prevalence of visually obvious lipoatrophy in pre-pubertal South African children on antiretroviral therapy is high. The amount of stavudine that children are exposed to needs review. Resources are needed to enable low-and-middle-income countries to provide suitable pediatric-formulated alternatives to stavudine-based pediatric regimens. The standard stavudine dose for children may need to be reduced. Diagnosis of lipoatrophy at an early stage is important to allow timeous antiretroviral switching to arrest progression and avoid stigmatization. Diagnosis using visual grading requires training and experience, and DXA and comprehensive anthropometry are not commonly available. A simple objective screening tool is needed to identify early lipoatrophy in resource-limited settings where specialized skills and equipment are not available.
authors.affiliation: Department of Paediatrics, Children's Infectious Diseases Clinical Research Unit (KID CRU), Tygerberg Children's Hospital, Stellenbosch University, Cape Town, South Africa. innes@sun.ac.za
authors.forename: Steve
authors.initials: S
authors.lastname: Innes
authors.forename: Mark F
authors.initials: MF
authors.lastname: Cotton
authors.forename: Richard
authors.initials: R
authors.lastname: Haubrich
authors.forename: Maria M
authors.initials: MM
authors.lastname: Conradie
authors.forename: Margaret
authors.initials: M
authors.lastname: van Niekerk
authors.forename: Clair
authors.initials: C
authors.lastname: Edson
authors.forename: Helena
authors.initials: H
authors.lastname: Rabie
authors.forename: Sonia
authors.initials: S
authors.lastname: Jain
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Sun
authors.forename: Ekkehard W
authors.initials: EW
authors.lastname: Zöllner
authors.forename: Stephen
authors.initials: S
authors.lastname: Hough
authors.forename: Sara H
authors.initials: SH
authors.lastname: Browne
mesh_terms: D015502:Absorptiometry, Photon; D050154:Adiposity; D019380:Anti-HIV Agents / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D015995:Prevalence; D012307:Risk Factors; D013019:South Africa; D018119:Stavudine / Q000009:adverse effects*; D013997:Time Factors
chemical_list: D019380:Anti-HIV Agents; D018119:Stavudine