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.

Background Perinatally-acquired HIV infection commonly causes stunting in children; how this affects bone and muscle development is unclear. We investigated differences in bone and muscle mass and muscle function between children with HIV (CWH) and uninfected children. Setting Cross-sectional study of CWH (6–16 years) receiving antiretroviral therapy (ART) for >6 months and similar aged children testing HIV-negative at primary health clinics in Zimbabwe. Methods From Dual-energy X-ray Absorptiometry (DXA) we calculated total-body less-head (TBLH) Bone Mineral Content (BMC) for lean mass adjusted-for-height (TBLH-BMC LBM ) Z-scores, and lumbar spine (LS) Bone Mineral Apparent Density (BMAD) Z-scores. Results The 97 CWH were older (mean age 12.7 vs. 10.0 years) and taller (mean height 142 cm vs. 134 cm) than 77 uninfected. However, stunting (height-for-age Z-score ≤ −2) was more prevalent in CWH (35% vs. 5%, p < 0.001). Among CWH, 15% had low LS-BMAD (Z-score ≤ −2) and 13% low TBLH-BMC LBM , vs. 1% and 3% respectively in those uninfected (both p ≤ 0.02). After age, sex, height and puberty adjustment, LS-BMAD was 0.33 SDs (95%CI -0.01, 0.67; p = 0.06) lower in CWH, with no differences by HIV status in TBLH-BMC LBM , lean mass (0.11 [−0.03, 0.24], p = 0.11) or grip strength (0.05 [−0.16, 0.27], p = 0.62). However, age at ART initiation was correlated with both LS-BMAD Z-score (r = −0.33, p = 0.001) and TBLH-BMC LBM Z-score (r = −0.23, p = 0.027); for each year ART initiation was delayed a 0.13 SD reduction in LS-BMAD was seen. Conclusion Size-adjusted low bone density is common in CWH. Delay in initiating ART adversely affects bone density. Findings support immediate ART initiation at HIV diagnosis.

IntroductionThe 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 analysisChildren 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 disseminationEthical 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.