# Longitudinal changes in bone mineral density among children living with HIV over 96 weeks following switch to second-line antiretroviral therapy in Uganda

## TL;DR

This study examines how switching to second-line HIV treatments affects bone health in Ugandan children over two years.

## Contribution

The study provides new insights into the longitudinal effects of second-line ART on bone mineral density in children living with HIV.

## Key findings

- Changes in bone mineral density were similar between TAF/FTC and standard-of-care regimens.
- Greater declines in BMD were linked to higher baseline BMD and prior nevirapine use.
- Smaller BMD declines were associated with higher fat mass and specific ART regimens like DRV/r, DTG, or ATV/r.

## Abstract

Long-term impact of antiretroviral therapy (ART) on bone health in children living with HIV (CLWH) remains uncertain. We aimed to determine associations of change in bone mineral density (BMD) among CLWH in Uganda in a 2-year prospective sub-study in the CHAPAS-4 randomized trial (ISRCTN22964075). CLWH aged 3–15 years switched to second-line ART including tenofovir alafenamide fumarate-emtricitabine (TAF/FTC) or standard-of-care (SOC) (abacavir (ABC) or zidovudine (ZDV) with dolutegravir (DTG), atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r) or lopinavir/ritonavir (LPV/r). BMD was assessed by dual-energy X-ray absorptiometry (DXA) at baseline, weeks 48 and 96 and bone turnover markers measured at baseline, week 24, 48, and 96. Robust regression analysis determined associations of BMD and bone turnover markers through week 96. Of 196 participants,167 contributed BMD measurements. Median (IQR) age was 9.9(7.0,12.3) years, 47% male, median (IQR) CD4 T-cell count 797(537,1140) cells/µl and mean (SD) viral load (log10 copies/ml) 4.3(0.8). Change in Procollagen type I N-terminal propeptide (PINP), C-terminal telopeptide of type I collagen (CTX) and height-adjusted (HA) BMD were similar between TAF/FTC and SOC. Greater declines in total-body-less-head (TBLH) BMD were associated with higher baseline TBLH (HA) BMD (Coef. -0.30,95% CI: -0.46, -0.15], p < 0.001) and first-line nevirapine (NVP) exposure (-0.25,95% CI: -0.43, -0.06, p = 0.009). Smaller TBLH HA BMD declines were associated with higher baseline fat-mass (0.06, 95% CI:0.01, 0.11, p = 0.021), higher lumbar spine (LS) HA BMD (0.17, 95% CI:0.03, 0.31, p = 0.015), DRV/r (0.46, p < 0.001,95% CI:0.21,0.71), DTG (0.26, p = 0.041,95% CI:0.01,0.51) or ATV/r (0.28, p = 0.026, 95% CI: 0.03, 0.52) use compared with LPV/r. Smaller declines in TBLH BMD were associated with higher baseline fat mass, higher LS HA BMD, and use of DRV/r, DTG, or ATV/r compared with LPV/r. These findings emphasize the importance of ART selection and body composition in supporting bone health among CLWH.