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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

The impact of vertical HIV infection on child and adolescent skeletal development in Harare, Zimbabwe (IMVASK Study): a protocol for a prospective cohort study
The impact of vertical HIV infection on child and adolescent skeletal development in Harare, Zimbabwe (IMVASK Study): a protocol for a prospective cohort study

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, epidemiology, paediatric radiology, tropical medicine
2044-6055
1-10
Rukuni, Ruramayi
c2632960-bd81-4238-b214-a6ec3121f899
Gregson, Celia L.
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Kahari, Cynthia
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Kowo, Farirayi
b1033b67-0e5f-4ab1-bff9-329920f9f72c
McHugh, Grace
49956d4d-ba9e-4bc8-84cc-07533f766c19
Munyati, Shungu
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Mujuru, Hilda
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Ward, Kathryn
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Filteau, Suzanne
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Rehman, Andrea M.
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Ferrand, Rashida A.
9441b7cd-4eb5-4665-aa69-357911fd2c87
Rukuni, Ruramayi
c2632960-bd81-4238-b214-a6ec3121f899
Gregson, Celia L.
30fae822-e733-4e67-b11a-e46dfb1b269a
Kahari, Cynthia
833e2734-f622-41cf-a877-5c0fa2a1d8dc
Kowo, Farirayi
b1033b67-0e5f-4ab1-bff9-329920f9f72c
McHugh, Grace
49956d4d-ba9e-4bc8-84cc-07533f766c19
Munyati, Shungu
8565399d-8ce9-4856-93e4-b1e27f7e2904
Mujuru, Hilda
91a774c1-d14c-462b-803b-50be5a7476be
Ward, Kathryn
39bd4db1-c948-4e32-930e-7bec8deb54c7
Filteau, Suzanne
9c7402f1-cd8b-4379-9414-61038a7572f9
Rehman, Andrea M.
70df2a8e-aa95-4942-ad10-4644280f13bf
Ferrand, Rashida A.
9441b7cd-4eb5-4665-aa69-357911fd2c87

Rukuni, Ruramayi, Gregson, Celia L., Kahari, Cynthia, Kowo, Farirayi, McHugh, Grace, Munyati, Shungu, Mujuru, Hilda, Ward, Kathryn, Filteau, Suzanne, Rehman, Andrea M. and Ferrand, Rashida A. (2020) The impact of vertical HIV infection on child and adolescent skeletal development in Harare, Zimbabwe (IMVASK Study): a protocol for a prospective cohort study. BMJ Open, 10 (2), 1-10, [e031792]. (doi:10.1136/bmjopen-2019-031792).

Record type: Article

Abstract

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.

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Accepted/In Press date: 2 January 2020
e-pub ahead of print date: 9 February 2020
Published date: 9 February 2020
Additional Information: Funding Information: 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). Publisher Copyright: © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.
Keywords: HIV & AIDS, epidemiology, paediatric radiology, tropical medicine

Identifiers

Local EPrints ID: 437816
URI: http://eprints.soton.ac.uk/id/eprint/437816
ISSN: 2044-6055
PURE UUID: 63b2f885-e50f-4ce2-9a35-257139fbf48e
ORCID for Kathryn Ward: ORCID iD orcid.org/0000-0001-7034-6750

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Date deposited: 19 Feb 2020 17:31
Last modified: 17 Mar 2024 03:40

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Contributors

Author: Ruramayi Rukuni
Author: Celia L. Gregson
Author: Cynthia Kahari
Author: Farirayi Kowo
Author: Grace McHugh
Author: Shungu Munyati
Author: Hilda Mujuru
Author: Kathryn Ward ORCID iD
Author: Suzanne Filteau
Author: Andrea M. Rehman
Author: Rashida A. Ferrand

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