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Biceps Skin-fold Thickness May Detect and Predict Early Lipoatrophy in HIV-infected Children

Innes, Steve MB ChB, MRCPCH, MPhil, PhD*; Schulte-Kemna, Eva MD; Cotton, Mark F. MB ChB, MMed, FCPaed, DTM&H, DCH, PhD*; Zöllner, Ekkehard Werner MBBCh, MMed, DCH, DTM&H, DPH; Haubrich, Richard MD§; Klinker, Hartwig MD, PhD; Sun, Xiaoying MSc; Jain, Sonia PhD; Edson, Clair MBBCh, DCH; van Niekerk, Margaret BSc(diet)**; Innes, Emily Ryan BSc(diet)**; Rabie, Helena MBBCh, MMed, FCPaed; Browne, Sara H. MD, MPH††

Pediatric Infectious Disease Journal: June 2013 - Volume 32 - Issue 6 - p e254–e262
doi: 10.1097/INF.0b013e3182814b30
HIV Reports

Background: The prevalence of potentially stigmatizing lipoatrophy in children receiving antiretroviral therapy in Southern Africa is high, affecting around a third of children. Early diagnosis of lipoatrophy is essential for effective intervention to arrest progression.

Methods: Prepubertal children receiving antiretroviral therapy were recruited from a hospital-based family HIV clinic in Cape Town and followed up prospectively. Lipoatrophy was identified and graded by consensus between 2 HIV pediatricians. A dietician performed anthropometric measurements of trunk and limb fat. Anthropometric measurements in children with and without lipoatrophy were compared using multivariable linear regression adjusting for age and gender. The most discerning anthropometric indicators of lipoatrophy underwent receiver operating characteristic curve analysis. The precision of anthropometric measurements performed by an inexperienced healthcare worker was compared with that of a research dietician.

Results: Of 100 recruits, 36 had lipoatrophy at baseline and a further 9 developed lipoatrophy by 15-month follow-up. Annual incidence of lipoatrophy was 12% (confidence interval [CI]: 5–20%) per person-year of follow-up. A biceps skin-fold thickness <5 mm at baseline had a sensitivity of 89% (CI: 67–100%) and a specificity of 60% (CI: 46–75%) for predicting development of lipoatrophy by 15-month follow-up. Negative and positive predictive values were 97% (CI: 91–100%) and 32% (CI: 14–50%).

Conclusion: Biceps skin-fold thickness <5 mm in prepubertal children exposed to thymidine analogue-based antiretroviral therapy may be a useful screening tool to identify children who are likely to develop lipoatrophy. The variation in precision of measurements performed by an inexperienced healthcare worker only marginally impacted performance.

From the *Children’s Infectious Diseases Clinical Research Unit, Tygerberg Children’s Hospital, and Department of Paediatrics, Stellenbosch University, Cape Town, South Africa; Universitätsklinikum Würzburg, Medizinische Klinik, Schwerpunkt Infektiologie, Würzburg, Germany; Department of Paediatrics, Division of Endocrinology, Stellenbosch University, Cape Town, South Africa; §Antiviral Research Centre; Biostatistics Research Center, Division of Biostatistics and Bioinformatics, University of California, San Diego, CA; Departments of Paediatrics and **Dietetics, Stellenbosch University, Cape Town, South Africa; and ††Department of Medicine, Division of Infectious Diseases, University of California, San Diego, CA.

Accepted for publication November 28, 2012.

The content of this publication does not necessarily reflect the views or policies of National Institute of Allergy and Infectious Diseases, nor does mention of trade names, commercial projects, or organizations imply endorsement by the US Government.

S.I. is currently receiving a Fogarty International Clinical Research Fellowship grant (#R24-TW007988-01), a pilot research grant (#P30 AI036214-16, subaward #10304442) from the University of California San Diego Centre for AIDS Research (CFAR) and a Southern Africa Consortium for Research Excellence grant (#WTX055734) from the Wellcome Trust. E.S.-K. received support from the National Research Foundation South Africa, the Deutschen Forschungsgemeinschaft (DFG) and the Bayerischen Bundesregierung (International Research Training Group Projekt 1522 “HIV/AIDS and Associated Infectious Diseases in South Africa”). M.F.C. is currently receiving a grant (#5U01AI069521-01 to 04) from the National Institute of Allergy and Infectious Diseases (NIAID) through the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT), a grant (#1U19AI53217-01) from NIAID through the Comprehensive International Plan for Research in AIDS and a grant (#USAID 674-A-00-09-00001-00) from United States Agency for International Development. The recruits on this study were not coenrolled in any IMPAACT trial. R.H. is currently receiving grants (#AI 27670 and #K24 AI064086) from NIAID through the San Diego AIDS Clinical Trials Group (ACTG) Clinical Trials Unit and the Antiviral Research Center, Department of Medicine, University of California San Diego (#AI36214; #P30-AI36214 and #AI69432). H.K. received support from the National Research Foundation South Africa, the DFG and the Bayerischen Bundesregierung (International Research Training Group Projekt 1522 “HIV/AIDS and Associated Infectious Diseases in South Africa”), the Bundesministerium für Wirtschaft und Technologie (# 03EGSBY044), and the Bundesministerium für Bildung und Forschung (#01 KG 0915). He reports receiving Board membership fees from Abbott, Bristol-Myers Squibb, Boehringer, Gilead, Janssen-Cilag and Merck Sharp & Dohme, and lecture fees from Bristol-Myers Squibb, Boehringer, Gilead, Merck Sharp & Dohme and Roche. S.H.B. is currently receiving grants (#P30-AI36214; #K08 AI62758 and #R43 AI093318-01). Database support was provided by the Vanderbilt Institute for Clinical and Translational Research (grant #1 UL1 RR024975 from National Center for Research Resources/NIH). The authors have no other funding or conflicts of interest to disclose.

Address for correspondence: Steve Innes, MB ChB, MRCPCH, MPhil, PhD, Children’s Infectious Diseases Clinical Research Unit, Tygerberg Children’s Hospital and Stellenbosch University, Cape Town, South Africa. E-mail: innes@sun.ac.za.

© 2013 Lippincott Williams & Wilkins, Inc.