Abstract
INTRODUCTION: Low bone mineral density (BMD) has been described in children and young people with perinatally acquired HIV (PHIV), which may be related to both traditional (e.g. low body mass index and malnutrition) and HIV-related risk factors (e.g. longstanding exposure to HIV and antiretroviral therapy [ART], with immune suppression, chronic immune activation and inflammation). Here, we evaluate BMD in a U.K. cohort of young people with PHIV by age and ART. METHODS: This longitudinal, observational study was conducted at a U.K. tertiary PHIV service between November 2018 and March 2022. Bone health was assessed in 130 individuals aged 15-19 (n = 50), 20-24 (n = 50) and 25 years and older (n = 30) by dual-energy X-ray absorptiometry, bone mineralization and turnover markers. Low BMD was defined as lumbar spine (LS) and/or femur-BMD z-score below -2, relative to age, sex and ethnicity-matched U.K. population-based normative controls. Two-year follow-up evaluation was performed in those aged 15-19 (n = 42) and 20-24 years (n = 43) at enrolment, which included a group who switched from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) ART at baseline. Bayesian logistic regression models examined predictors of low BMD and the effect of ART-backbone on BMD accrual. RESULTS: At baseline, 57% were female and 82% of black ethnicity, with 31 (24%) on TDF-ART. Sixteen (12%) had low baseline BMD. Over a median follow-up duration of 26 (interquartile range [IQR] 25-29) months, BMD accrual was lower-than-expected in those aged 15-19 years (mean change LS-BMD z-score -0.15 (standard deviation [SD] 0.44)), when compared to normative controls. No associations were seen with HIV parameters or the ART regimen. Participants who switched to TAF-ART had similar BMD accrual 26 (IQR 24-32) months post switch, when compared to those on non-TAF/TDF-ART (mean change LS-BMD z-score TAF -0.01 [SD 0.41] vs. non-TAF/TDF -0.03 [SD 0.54]). CONCLUSIONS: While rates of low BMD were reassuringly low in this cohort, lower-than-expected BMD accrual was observed in younger individuals, relative to normative controls. Overall, BMD accrual on TAF-ART was non-inferior to non-TAF/TDF-ART.