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The IMpact of Vertical HIV infection on child and Adolescent SKeletal development in Harare, Zimbabwe (IMVASK Study): a protocol for a prospective cohort study
  1. Ruramayi Rukuni1,2,
  2. Celia Gregson3,4,
  3. Cynthia Kahari2,5,
  4. Farirayi Kowo6,
  5. Grace McHugh2,
  6. Shungu Munyati2,
  7. Hilda Mujuru7,
  8. Kate Ward8,
  9. Suzanne Filteau9,
  10. Andrea M Rehman10,
  11. Rashida Ferrand11
  1. 1 Clinical Research Department, London School of Hygiene and Tropical Medicine, London, UK
  2. 2 Biomedical Research and Training Institute, Harare, Zimbabwe
  3. 3 Musculoskeletal Research Unit, University of Bristol, Bristol, UK
  4. 4 Older Person's Unit, Royal United Hospital NHS Trust, Bath, UK
  5. 5 Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
  6. 6 Department of Radiology, University of Zimbabwe, Harare, Zimbabwe
  7. 7 Department of Paediatrics and Child Health, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe
  8. 8 Lifecourse Epidemiology Unit, MRC, Southampton, UK
  9. 9 Population Health, London School of Hygiene & Tropical Medicine, London, UK
  10. 10 Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
  11. 11 Clinical Research Department, London School of Hygiene and Tropical Medicine, London, UK
  1. Correspondence to Dr Ruramayi Rukuni; ruramayi.rukuni{at}lshtm.ac.uk

Abstract

Introduction The scale-up of antiretroviral therapy (ART) across sub-Saharan Africa (SSA) has reduced mortality so that increasing numbers of children with HIV (CWH) are surviving to adolescence. However, they experience a range of morbidities due to chronic HIV infection and its treatment. Impaired linear growth (stunting) is a common manifestation, affecting up to 50% of children. However, the effect of HIV on bone and muscle development during adolescent growth is not well characterised. Given the close link between pubertal timing and musculoskeletal development, any impairments in adolescence are likely to impact on future adult musculoskeletal health. We hypothesise that bone and muscle mass accrual in CWH is reduced, putting them at risk of reduced bone mineral density (BMD) and muscle function and increasing fracture risk. This study aims to determine the impact of HIV on BMD and muscle function in peripubertal children on ART in Zimbabwe.

Methods and analysis Children with (n=300) and without HIV (n=300), aged 8–16 years, established on ART, will be recruited into a frequency-matched prospective cohort study and compared. Musculoskeletal assessments including dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, grip strength and standing long jump will be conducted at baseline and after 1 year. Linear regression will be used to estimate mean size-adjusted bone density and Z-scores by HIV status (ie, total-body less-head bone mineral content for lean mass adjusted for height and lumbar spine bone mineral apparent density. The prevalence of low size-adjusted BMD (ie, Z-scores <−2) will also be determined.

Ethics and dissemination Ethical approval for this study has been granted by the Medical Research Council of Zimbabwe and the London School of Hygiene and Tropical Medicine Ethics Committee. Baseline and longitudinal analyses will be published in peer-reviewed journals and disseminated to research communities.

  • HIV & AIDS
  • tropical medicine
  • paediatric radiology
  • epidemiology
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This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

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Footnotes

  • Twitter @celiagregson

  • Contributors RR, RF and CG codesigned the study. RR wrote the study protocol and was responsible for journal selection and preparation of the first draft of this article as the principal author. CK contributed to the development of the peripheral quantitative computed tomography protocols. FK contributed to the development of the bone age analysis protocols. KW provided scan protocols, contributed to the study design, and gave methodological input regarding bone density size-adjustment and analysis. AMR contributed to the study design, in particular, sampling strategy, sample size calculation and the statistical analysis plan. SF provided advice regarding the development of nutritional assessment tools. GM, SM and HM advised on study conduct and provided study oversight. All authors reviewed and provided feedback on the manuscript prior to submission.

  • Funding This study is funded by the Wellcome Trust UK. RR is funded by Wellcome Trust UK grant number 206764/Z/17/Z. CK is funded by a National Institute of Health Fogarty Trent Fellowship (grant number 2D43TW009539-06). RF is funded by Wellcome Trust grant number 206316/Z/17/Z. Global challenges research funding from the University of Bristol established the sub-Saharan African MuSculOskeletal Network (SAMSON) enabling the provision of peripheral quantitative computed tomography in Zimbabwe for this study. AMR is additionally supported by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement which is also part of the EDCTP2 programme supported by the European Union grant reference (MR/R010161/1).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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