Older age at initiation of antiretroviral therapy predicts low bone mineral density in children with perinatally-infected HIV in Zimbabwe

Abstract

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.

Nutritional status and dietary diversity of school-age children living with HIV: a cross-sectional study in Phnom Penh, Cambodia

“…This nding is similar to results of a recent study conducted in Thailand, which demonstrated that the younger the children at ART initiation, the greater the effect on height-growth velocity regardless of the ART regimen [35]. Another recent study revealed that HIV infection was associated with not only stunting but also low lumbar spine bone density among children living with HIV in Zimbabwe and that younger age at initiation of ART predicted high bone mineral density [36]. There are additional studies which stress the importance of initiating ART before irreversible stunting has occurred [37].…”

Nutritional status and dietary diversity of school-age children living with HIV: a cross sectional study in Phnom Penh, Cambodia

“…This finding is similar to results of a recent study conducted in Thailand, which demonstrated that the younger the children at ART initiation, the greater the effect on height-growth velocity regardless of the ART regimen [Traisathit]. Another recent study revealed that HIV infection was associated with not only stunting but also low lumbar spine bone density among children living with HIV in Zimbabwe and that younger age at initiation of ART predicted high bone mineral density [30]. There are additional studies which stress the importance of initiating ART before irreversible stunting has occurred [31].…”

Chronic comorbidities in children and adolescents with perinatally acquired HIV infection in sub-Saharan Africa in the era of antiretroviral therapy

“…A recent study from Zimbabwe showed reduced size-adjusted (Z-Score ≤ -2.0) lumbar spine total-body-less head bone density measurements in 15% and 13% of CWHIV aged 8 to 16 years taking ART. 48 Notably, this study used 'gold-standard' size adjustment methods for analysing dual X-ray absorptiometry scans which, if ignored, underestimate bone density in stunted children. 49 Certain ART drugs such as TDF may cause accelerated bone loss, likely aggravated by both low body mass and vitamin D deficiency.…”

“…34 While studies have reported an association of TDF with lower bone density in CWHIV, this association may not be sustained longterm and longitudinal studies from SSA are needed to determine the impact of TDF on bone health in children. 34,48,50 Additional factors, prevalent among CWHIV, can further compromise bone health, including low muscle mass, poor nutrition, inadequate dietary calcium, vitamin D deficiency and the HIV-associated pro-inflammatory milieu. [51][52][53] Muscle strength and bone strength are closely related; muscles exert forces on bone resulting in bone adaptation in size and strength.…”

“…In the Zimbabwe study, CWHIV starting ART after the age of eight years had, on average, at least a one standard deviation lower size-adjusted lumbar spine bone density. 48 This level of bone density reduction doubles fracture risk in adults. 58 Given the late average age at ART initiation of CWHIV in SSA, these findings are concerning.…”