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Insulin Resistance and Markers of Inflammation in HIV-infected Ugandan Children in the CHAPAS-3 Trial

Dirajlal-Fargo, Sahera DO*†; Musiime, Victor PhD‡§; Cook, Adrian MSc; Mirembe, Grace MMED; Kenny, Julia BM BCh¶‖; Jiang, Ying MS*; Debanne, Sara PhD*; Klein, Nigel PhD; McComsey, Grace A. MD*†

Pediatric Infectious Disease Journal: August 2017 - Volume 36 - Issue 8 - p 761–767
doi: 10.1097/INF.0000000000001544
HIV Reports

Background: Few studies have investigated metabolic complications in HIV-infected African children and their relation with inflammation.

Methods: We compared baseline and changes in insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR)] and in markers of inflammation over 48 weeks, in a subset of antiretroviral therapy (ART)–naive Ugandan children from the Children with HIV in Africa-Pharmacokinetics and Adherence/Acceptability of Simple Antiretroviral Regimens trial randomized to zidovudine-, stavudine- or abacavir (ABC)–based regimen. Nonparametric methods were used to explore between-group and within-group differences, and multivariable analysis to assess associations of HOMA-IR.

Results: One-hundred eighteen children were enrolled, and median age (interquartile range) was 2.8 years (1.7–4.3). Baseline median HOMA-IR (interquartile range) was 0.49 (0.38–1.07) and similar between the arms. At week 48, median relative changes in HOMA-IR were 14% (−29% to 97%) in the zidovudine arm, −1% (−30% to 69%) in the stavudine arm and 6% (−34% to 124%) in the ABC arm (P ≤ 0.03 for all the arms compared with baseline, but P = 0.90 for between-group differences). Several inflammation markers significantly decreased in all study arms; soluble CD14 increased on ABC and did not change in the other 2 arms. In multivariate analysis, only changes in soluble CD163 were positively associated with HOMA-IR changes.

Conclusions: In ART-naive Ugandan children, HOMA-IR changed significantly after 48 weeks of ART and correlated with monocyte activation.

From the *Case Western Reserve University, and†Rainbow Babies and Children’s Hospital, Cleveland, Ohio; Joint Clinical Research Centre, and §Makerere University College of Health Sciences, Kampala, Uganda; MRC Clinical Trials Unit University College, and Institute of Child Health University College, London, United Kingdom.

Accepted for publication September 28, 2016.

S.D-F. and G.A.M. designed the research, wrote the manuscript, assisted with data analysis and obtained funding. V.M., A.C., G.M., J.K. and N.K. conducted research (CHAPAS-3 trial team) and reviewed/edited the manuscript. Y.J. and S.D. performed the statistical analysis.

The work in this analysis was supported by an internal grant from Rainbow Babies and Children’s Hospital, the Clinical & Translational Science Collaborative of Cleveland NIH grant (UL1TR000439) and by the Infectious Diseases and Immunology Institute, Case Western Reserve University (to S.D-F.). CHAPAS-3 was funded by the European Developing Countries Clinical Trials Partnership (EDCTP) (IP.2007.33011.006), the Medical Research Council (MRC), United Kingdom, the Department for International Development (DfID), United Kingdom and the Ministerio de Sanidad y Consumo Spain. Cipla Ltd. donated first-line antiretroviral drugs.

S.D. sits on the Data Safety Monitoring Board (DSMB) for clinical trials of Johnson and Johnson. G.A.M. served as a consultant for Bristol Meyer Squibb (BMS), Gilead, VIIV, GlaxoSmithKline (GSK), ICON, Pfizer and has received research funding from Bristol-Myers Squibb, VIIV and Gilead. The other authors have no conflicts of interest to disclose.

Address for correspondence: Grace A. McComsey, MD, FIDSA, Case Western Reserve University School of Medicine, 2061 Cornell Rd, Mail stop: 5083, Cleveland, OH. E-mail:

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