Patterns of linear growth among children and adolescents living with HIV on antiretroviral therapy in Zimbabwe and Zambia

Abstract

Background: Adolescents with HIV (AWH) frequently exhibit impaired growth, which manifests as stunting and wasting. We studied trajectories in leg-length (appendicular), sitting (axial), and standing height among AWH on antiretroviral therapy (ART), determining peak height velocity (PHV) and age at PHV (aPHV).

Methods: Analyses used VITALITY trial data from Zimbabwe and Zambia (PACTR20200989766029), which recruited AWH (11-19 years) established on ART to determine whether vitamin D₃/calcium supplementation improves bone health. The study enrolled participants between January and December 2021. Weight-for-age and height-for-age z-scores (WAZ/HAZ) were calculated from 12-weekly anthropometry over 96 weeks. Height trajectory analyses used SuperImposition by Translation And Rotation (SITAR) methods adjusting for height, tempo (aPHV) and velocity. Linear associations between vitamin D/calcium supplementation, HIV-specific factors, WAZ, HAZ, and SITAR parameters were determined.

Results: Overall, 842 participants (53·2% female; median age 15·5 [IQR:13·2-17·9] years), were taking ART for median 9·8(IQR:6·3-12·3) years. Mean(SD) HAZ was 1·21(1·05) in females, -1·68(1·05) in males. Overall, 251(29·8%) AWH were stunted (HAZ < -2) and 253(30%) wasted (WAZ < -2). Standing, appendicular and axial aPHVs were: Female 13·4, 13·3, 13·9 years; Males 15·3, 15·0, 15·8 years. Unsuppressed viral-load(VL) and delayed ART initiation (age > 4-years) were associated with later aPHV and shorter axial height in females. In all, unsuppressed VL had a more negative effect on aPHV for axial (Females: β = 0·39 years [95%CI:0·12,0·65]; Males: β = 0·45 [95%CI:0·10,0·80]) than appendicular growth (Females: β = 0.31 [95%CI 0·08,0·53]; Males: β = 0·2 [95%CI:-0·17,0·56]). Conversely, delayed ART initiation was more negatively related to aPHV for appendicular (Females: β = 0·25 [95% CI:0·08,0·43]; Males: β = 0·63 [95%CI:0·32, 0·93] than axial growth (Females: β = 0·13 [95%CI:-0·08,0·34]; Males: β = 0·56 [95%CI:0·28,0·86]. Lower HAZ and WAZ were associated with lower height, later aPHV and lower PHV. At 48-week vitamin-D₃/calcium supplementation had no effect on the growth pattern.

Conclusion: Unsuppressed viral load and delayed ART-initiation predicted later aPHV. Stunting and wasting were associated with attenuated growth velocity and later aPHV. Adolescents with HIV experience persistent linear growth impairments, potentially persisting into adulthood.

Trial registration: (PACTR20200989766029|| http://www.pactr.org/ ); First registered on 03/09/2020.

Keywords: Adolescence; Africa; Antiretroviral therapy; HIV; Peak velocity; Puberty; SITAR.

Fig. 1

Axial, appendicular and standing height SITAR growth curves by sex, fitted with the mean SITAR curve. Legend: Crude individual growth curves (in grey) for axial (top row), appendicular (middle row), and standing heights (bottom row) fitted with the mean SITAR growth curve (dashed black lines) for female (left) and males (right)

Fig. 2

Mean and velocity curves for axial, appendicular and standing height for females and males. Legend: The top and bottom rows are showing mean and velocity curves respectively for standing (black), appendicular (purple) and axial (yellow) height

Fig. 3

Univariable linear regression models [β (95% CI)] for the association between demographic and anthropometry z-scores and SITAR growth parameters [size, timing of puberty (tempo) and velocity] showing a beta [95% CI] effect size. Legend: A forest plot showing univariate linear associations between dietary intake, socioeconomic status, HIV factors and malnutrition indicators with SITAR growth parameters [size (left), tempo (middle) and velocity (right) for appendicular (green), axial (orange) and standing (purple) heights. SES: Socioeconomic status; TDF; Tenofovir disoproxil fumarate; ART: Antiretroviral therapy; BMI: Body mass index; SD: Standard deviation