The IMpact of Vertical HIV infection on child and Adolescent SKeletal development in Harare, Zimbabwe (IMVASK Study): a protocol for a prospective cohort study

Rukuni, Ruramayi; Gregson, Celia L; Mukwasi-Kahari, Cynthia; Kowo, Farirayi; McHugh, Grace; Munyati, Shungu; Mujuru, Hilda; Ward, Kate; Filteau, Suzanne; Rehman, Andrea M.; Ferrand, Rashida A

doi:10.1136/bmjopen-2019-031792

Cited by 16 publications

(17 citation statements)

References 50 publications

(57 reference statements)

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“…We did a cross-sectional study using baseline DXA bone measurements from the IMVASK study, which is a prospective cohort study on the impact of vertical HIV infection on child and adolescent skeletal development in Harare, Zimbabwe. The IMVASK protocol has been published elsewhere (ISRCTN registry ISRCTN12266984) 11 and 12-month follow-up has been completed. Children aged 8–16 years with HIV were recruited from outpatient HIV clinics at the only two public sector general hospitals in Harare (Parirenyatwa General Hospital and Harare Central Hospital).…”

Section: Methodsmentioning

confidence: 99%

Section: Study Design and Participantsmentioning

confidence: 99%

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Effect of HIV infection on growth and bone density in peripubertal children in the era of antiretroviral therapy: a cross-sectional study in Zimbabwe

Rukuni

Rehman

Mukwasi-Kahari

et al. 2021

The Lancet Child & Adolescent Health

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Background Faltered linear growth and pubertal delay, which are both common in children with HIV in sub-Saharan Africa, might affect adolescent bone accrual and future fragility fracture risk. We investigated the association of HIV with bone density adjusted for skeletal size in peripubertal children in Zimbabwe. MethodsWe did a cross-sectional study of baseline data from the IMVASK cohort, which enrolled children aged 8-16 years with HIV who had been taking antiretroviral therapy (ART) for at least 2 years, and children of the same age without HIV. Children with HIV were recruited from public sector HIV clinics at Parirenyatwa General Hospital and Harare Central Hospital (Harare, Zimbabwe), and children without HIV were recruited from six schools in the same suburbs that the hospitals serve. Sociodemographic, clinical, and anthropometric data were collected. Dual-energy X-ray absorptiometry (DXA) was used to measure the bone outcomes of total-body less-head bone mineral content for lean mass adjusted for height (TBLH-BMC LBM ), and lumbar spine bone mineral apparent density (LS-BMAD), and we assessed the prevalence of low TBLH-BMC LBM and low LS-BMAD (defined by Z-scores of less than -2•0). Size adjustment techniques were used to overcome the size dependence of DXA measurement. We used linear regression models, with multiple imputation for missing data, to assess relationships between risk factors and TBLH-BMC LBM and LS-BMAD Z-scores in children with and without HIV. Findings We recruited 303 children with HIV (mean age 12•4 years [SD 2•5]; 151 [50%] girls) and 306 children without HIV (mean age 12•5 years [SD 2•5]; 155 [51%] girls). In children with HIV, median age of HIV diagnosis was 3•0 years (IQR 1•2-5•8), and median ART duration was 8•1 years (6•2-9•5); for 102 (34%) children, ART included tenofovir disoproxil fumarate (TDF). Children with HIV had a higher prevalence of low TBLH-BMC LBM Z-score than children without HIV (29 [10%] of 279 children with available data vs 18 [6%] of 292 with available data; p=0•066) and a higher prevalence of low LS-BMAD Z-score (40 [14%] of 279 vs 17 [6%] of 293 with available data; p=0•0007). HIV and male sex were associated with earlier pubertal (Tanner) stage. The negative associations between HIV and Z-scores for TBLH-BMC LBM and LS-BMAD were more pronounced with pubertal maturation, particularly in girls. Among children with HIV, TDF exposure and orphanhood were associated with lower TBLH-BMC LBM Z-score in confounder-adjusted analysis. Current TDF use (vs non-TDF-based ART) was associated with a reduction in TBLH-BMC LBM Z-score of 0•41 (95% CI 0•08-0•74; p=0•015) and in LS-BMAD Z-score of 0•31 (0•08-0•69; p=0•12). Interpretation Despite ART, HIV is associated with substantial skeletal deficits towards the end of puberty. The extent of bone deficits associated with TDF and its widespread use in children in sub-Saharan Africa are a concern for future adult fracture risk. Funding Wellcome Trust.

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Section: Methodsmentioning

confidence: 99%

Section: Study Design and Participantsmentioning

confidence: 99%

Effect of HIV infection on growth and bone density in peripubertal children in the era of antiretroviral therapy: a cross-sectional study in Zimbabwe

Rukuni

Rehman

Mukwasi-Kahari

et al. 2021

The Lancet Child & Adolescent Health

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“…The effect size is based on the IMVASK study of 188 adolescents aged 11-17 living with HIV and 199 HIV-negative controls of the same age. The difference in TBLH-BMC LBM Z-score between groups increased with age [24]. We used a weighted analysis with 16-year-olds and 17-year-olds having a doubled weight, representing the 18-19 age group who were not recruited in the IMVASK study.…”

Section: Sample Size {14}mentioning

confidence: 99%

Vitamin D3 and calcium carbonate supplementation for adolescents with HIV to reduce musculoskeletal morbidity and immunopathology (VITALITY trial): study protocol for a randomised placebo-controlled trial

Chisenga

McHugh

et al. 2022

Trials

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Background Of the 2 million children living with HIV globally, 90% live in sub-Saharan Africa. Despite antiretroviral therapy, longstanding HIV infection is associated with several chronic complications in children including growth failure, particularly stunting and delayed puberty. Vitamin D deficiency, which is highly prevalent among children living with HIV in sub-Saharan Africa, has a further adverse impact on bone health. This trial aims to establish whether supplementation with vitamin D3 and calcium carbonate improves musculoskeletal health among peripubertal children living with HIV. Methods/design We will conduct an individually randomised, double-blinded, placebo-controlled trial of weekly high-dose vitamin D3 (20,000 IU) plus daily calcium carbonate (500mg) supplementation for 48 weeks. Eight hundred and forty children living with HIV aged 11–19 years taking ART for ≥6 months will be enrolled and followed up for 96 weeks. The primary outcome is total body less-head bone mineral content for lean mass adjusted for height (TBLH-BMCLBM) Z-score at 48 weeks, measured by dual-energy X-ray absorptiometry (DEXA). Secondary outcomes are DEXA-measured lumbar spine bone mineral apparent density Z-score, number of respiratory infections, lean muscle mass and grip strength at 48 and 96 weeks and TBLH-BMCLBMZ-scores at 96 weeks. Sub-studies will investigate the effect of the intervention on vitamin D3 pathway metabolites and markers of bone turnover, intestinal microbiota, and innate and acquired immune function. Discussion This is the largest trial to date of vitamin D supplementation in children living with HIV. Intervening to address deficits in bone accrual in childhood is critical for optimising adolescent and early adult bone health and prevention of later adult osteoporotic fractures. Trial results will draw attention to the need to screen for and treat long-term comorbidities in children living with HIV in resource-limited settings. Trial registration Pan African Clinical Trials Registry PACTR20200989766029. Registered on 3 September 2020

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“…The effect size is based on the IMVASK study of 188 adolescents aged 11-17 living with HIV and 199 HIV negative controls of the same age. The difference in TBLH-BMC LBM Z-score between groups increased with age (25). We used a weighted analysis with 16-year-olds and 17-year-olds having a doubled weight, representing the 18-19 age group who were not recruited in the IMVASK study.…”

Section: Sample Size {14}mentioning

confidence: 99%

Vitamin D3 and calcium carbonate supplementation for adolescents with HIV to reduce musculoskeletal morbidity and immunopathology (VITALITY Trial): study protocol for a randomised placebo-controlled trial

Chisenga

McHugh

et al. 2021

Preprint

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Background: Of the 2 million children living with HIV globally, 90% live in sub-Saharan Africa. Despite antiretroviral therapy, longstanding HIV infection is associated with several chronic complications in children including growth failure, particularly stunting and delayed puberty. Vitamin D deficiency, which is highly prevalent among children living with HIV in sub-Saharan Africa, has further adverse impact on bone health. This trial aims to establish whether supplementation with vitamin D 3 and calcium carbonate improves musculoskeletal health among peripubertal children living with HIV. Methods/design: We will conduct an individually randomised, double-blinded, placebo-controlled trial of weekly high-dose vitamin D 3 (20000iu) plus daily calcium carbonate (500mg) supplementation for 48 weeks. 840 children living with HIV aged 11-19 years taking ART for ≥6 months will be enrolled and followed up for 96 weeks. The primary outcome is total body less-head bone mineral content for lean mass adjusted for height (TBLH-BMC LBM ) Z-score at 48 weeks, measured by dual-energy x-ray absorptiometry (DEXA). Secondary outcomes are DEXA-measured Lumbar Spine Bone Mineral Apparent Density Z-score, number of respiratory infections, lean muscle mass and grip-strength at 48 and 96 weeks, and TBLH-BMC LBM Z-scores at 96 weeks. Sub studies will investigate the effect of the intervention on vitamin D 3 pathway metabolites and markers of bone turnover, intestinal microbiota, and innate and acquired immune function. Discussion: This is the largest trial to date of vitamin D supplementation in children living with HIV. Intervening to address deficits in bone accrual through childhood is critical for optimising adolescent and early adult bone health, and prevention of later adult osteoporotic fractures. Trial results will draw attention to the need to screen for and treat long-term comorbidities in children living with HIV in resource-limited settings.Trial registration: Pan African Clinical Trials Registry ID: PACTR20200989766029. Date ofregistration: 3 September 2020. URL of trial registry record: https://pactr.samrc.ac.za

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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

Cited by 16 publications

References 50 publications

Effect of HIV infection on growth and bone density in peripubertal children in the era of antiretroviral therapy: a cross-sectional study in Zimbabwe

Effect of HIV infection on growth and bone density in peripubertal children in the era of antiretroviral therapy: a cross-sectional study in Zimbabwe

Vitamin D3 and calcium carbonate supplementation for adolescents with HIV to reduce musculoskeletal morbidity and immunopathology (VITALITY trial): study protocol for a randomised placebo-controlled trial

Vitamin D3 and calcium carbonate supplementation for adolescents with HIV to reduce musculoskeletal morbidity and immunopathology (VITALITY Trial): study protocol for a randomised placebo-controlled trial

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