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

Abstract

Objectives: :To determine how muscle strength, power, mass, and density (i.e. quality) differ between children living with HIV (CWH) and those uninfected, and whether antiretroviral therapy (ART) regime is associated with muscle quality. Design: :A cross-sectional study in Harare, Zimbabwe. Methods: :The study recruited CWH aged 8–16years, taking ART for ≥2years, from HIV clinics, and HIV-uninfected children from local schools. Muscle outcomes comprised grip strength measured by hand-held Jamar dynamometer, lower-limb power measured by standing long-jump distance, lean mass measured by dual-energy X-ray absorptiometry, and muscle density (reflecting intramuscular fat) by peripheral quantitative computed tomography. Linear regression calculated adjusted mean differences (aMD) by HIV status. Results: :Overall, 303 CWH and 306 without HIV, had mean(SD) age 12.5(2.5) years, BMI 17.5(2.8), with 50% female. Height and fat mass were lower in CWH, mean differences(SE) 7.4(1.1)cm and 2.7(0.4)kgs, respectively. Male CWH had lower grip strength (aMD 2.5[1.1,3.9]kg, P < 0.001), long-jump distance (7.1[1.8,12.5]cm, P = 0.006), muscle density (0.58[0.12,1.05]mg/cm3, P = 0.018, but not lean mass 0.06[-1.08,1.21]kg, P = 0.891) versus boys without HIV; differences were consistent but smaller in females. Mediation analysis suggested the negative effect of HIV on jumping power in males was partially mediated by muscle density (P = 0.032). CWH taking tenofovir disoproxil fumarate (TDF) had lower muscle density (0.56[0.00,1.13]mg/cm3, P = 0.049) independent of fat mass, than CWH on other ART. Conclusions: :Perinatally-acquired HIV is associated, particularly in males, with reduced upper and lower-limb muscle function, not mass. Intra-muscular fat (poorer muscle quality) partially explained reductions in lower-limb function. TDF is a novel risk factor for impaired muscle quality.

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,…”

“…In addition to that, studies that aimed to investigate the relationship between HIV infection/ART use and the health-related physical fitness components showed changes in the body fat distribution [91,104,194,264], reduction in the bone mass [15,84,108,124,209,262] and fat-free mass [8,102]. However, only 12.2% (n = 30) of the studies investigated more than one the health-related physical fitness component [21][22][23][24][25][26][27][28][29][30][31]33,34,41,47,50,52,106,110,112,116,192,196,[221][222][223]226,230,233,238] and no study that investigated the relationship between the health-related physical fitness components was found. Muscular strength/endurance is directly associated with the amount of muscle fibers-that is, related to the amount of fat-free mass, specifically muscle tissue, as well as cardiorespiratory fitness-is directly associated with the amount of type I (oxidative) muscle fibers …”

“…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].…”