Impaired Bone Architecture in Peripubertal Children With HIV, Despite Treatment With Antiretroviral Therapy: A Cross-Sectional Study From Zimbabwe

Abstract

HIV infection has multi-system adverse effects in children, including on the growing skeleton. We aimed to determine the association between chronic HIV infection and bone architecture (density, size, strength) in peripubertal children. We conducted a cross-sectional study of children aged 8 to 16 years with HIV (CWH) on antiretroviral therapy (ART) and children without HIV (CWOH) recruited from schools and frequency-matched for age strata and sex. Outcomes, measured by tibial peripheral quantitative computed tomography (pQCT), included 4% trabecular and 38% cortical volumetric bone mineral density (vBMD), 4% and 38% cross-sectional area (CSA), and 38% stress-strain index (SSI). Multivariable linear regression tested associations between HIV status and outcomes, stratified by sex and puberty (Tanner 1-2 versus 3-5), adjusting for age, height, fat mass, physical activity, and socioeconomic and orphanhood statuses. We recruited 303 CWH and 306 CWOH; 50% were female. Although CWH were similar in age to CWOH (overall mean AE SD 12.4 AE 2.5 years), more were prepubertal (ie, Tanner 1; 41% versus 23%). Median age at ART initiation was 4 (IQR 2-7) years, whereas median ART duration was 8 (IQR 6-10) years. CWH were more often stunted (height-for-age Z-score <À2) than those without HIV (33% versus 7%). Both male and female CWH in later puberty had lower trabecular vBMD, CSA (4% and 38%), and SSI than those without HIV, whereas cortical density was similar. Adjustment explained some of these differences; however, deficits in bone size persisted in CWH in later puberty (HIV*puberty interaction p = 0.035 [males; 4% CSA] and p = 0.029 [females; 38% CSA]). Similarly, puberty further worsened the inverse association between HIV and bone strength (SSI) in both males (interaction p = 0.008) and females (interaction p = 0.004). Despite long-term ART, we identified deficits in predicted bone strength in those living with HIV, which were more overt in the later stages of puberty. This is concerning, as this may translate to higher fracture risk later in life.

Perinatal HIV infection is associated with deficits in muscle function in children and adolescents in Zimbabwe

“…Muscle and bone function as an integrated unit; muscle development influences bone development and vice versa [6]. We have previously identified deficits in bone mass [4] and predicted bone strength [49] in CWH, which were more overt in the later stages of puberty, mirroring the findings in this study. This raises the possibility that either HIV-associated bone deficits are (at least in part) a function of muscle deficits, or vice versa.…”

Health-Related Physical Fitness Evaluation in HIV-Diagnosed Children and Adolescents: A Scoping Review

“…The relationship between body composition and the HIV infection/ART use has been the studies main focus, since the beginning of the health-related physical fitness components investigation in HIV-diagnosed children and adolescents, primarily to understand alterations in growth pattern and nutritional status [7][8][9][10][11][12][13][14][15][16][17] and most recently to investigate modifications in body composition such as changes in fat mass distribution [18], alterations in bone mass [19,20] and reduction in muscle mass [21]. In the early 2000s, research began on the cardiorespiratory fitness [22,23], followed by the beginning of the research into muscular strength/endurance in the mid-2000s [27,28] and the beginning of the research into flexibility in 2010 [28], with the aim to investigate the relationship between the HIV infection/ART use and reduce cardiorespiratory fitness [22,23], low muscular strength/endurance [27,28] and flexibility [28].…”

“…Observing the aim of the studies, the results of the present scoping review reflect a broad descriptive investigation of differences between HIV-diagnosed populations and HIV non diagnosed peers [11,19,21,[23][24][25][26]29,30,38,51,73,, prevalences related to health-related physical fitness components [12,[117][118][119][120][121][122][123][124] and different associations [7,8,10,14,15,18,20,22,27,31,33,36,37,[39][40][41][42][43]45,47, between health-related physical fitness components and variables such as the HIV infection status (viral load, CD4 and CD8 lymphocyte count and immunosuppression status) [8,45,134,150] and use of different ART regimens [19,…”

“…Physical activity was investigated through different aims such as to investigate differences between HIV-diagnosed group compared to non-diagnosed groups [19,21,25,29,31,40,51,87,88,95,[98][99][100]106,108,109,112,115,143,198,204,234], to investigate the association between health-related physical fitness and physical activity level [18,29,33,42,95,99,100,124,197,210,227,238] and to adjust models through physical activity [18,36,37,42,230,231,233,238]. In addition to the assumption that improvements in physical activity level can result in improvements in health-related physical fitness components [48,49,53], it follows that physical activity can moderate the relationship between HIV infection/ART use and the health-related physical...…”

“…The investigation of health-related physical fitness in children and adolescents has been widely used to identify and understand those possible adverse effects of HIV infection/ART use such as changes in body composition (alterations in body fat distribution, reduction in bone mineral content and fat-free mass) [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]; reduced cardiorespiratory fitness [22][23][24][25][26]; reduced muscular strength/endurance [26][27][28][29][30]; and reduced flexibility [24,26,31]. However, studies that investigated HIV-diagnosed children and adolescents ended up developing their own methods/protocols for evaluating the health-related physical fitness [32][33][34][35] and also used empirical cut-points for physical fitness tests to classify the participants [19,[36][37][38][39][40][41][42]. This lack of standardization limits the comparison between studies and the direction of future studies.…”