Background:
Youth living with perinatally acquired HIV (YPaHIV) have multiple risk factors for low bone mineral density (BMD); early years malnutrition, impaired growth, delayed puberty, and the cumulative effects of antiretroviral therapy (ART) including tenofovir disoproxil fumarate (TDF). Tenofovir alafenamide (TAF) is recommended as an alternative to TDF in those < 25 years due to an improved safety profile. We present longitudinal data on BMD accrual in YPaHIV on TAF vs non-TAF, non-TDF ART.
Methods:
A longitudinal, observational study (London U.K.) evaluated bone health in YPaHIV aged 15-19 years (n=50), 20-24 (n=50) and 25+ (n=30) by dual-energy X-ray absorptiometry, bone biochemistry and turnover markers, vitamin D and parathyroid hormone (PTH) with 2-year follow up evaluation in 15-19 years (n=42) and 20-24 (n=43). Abnormal BMD was classified as osteopenia (Z/T score < -1) or osteoporosis (Z/T score < -2). T-tests compared results between TAF and non-TAF ART. Linear regression identified factors associated with low BMD and 2-year BMD accrual.
Results:
At baseline 74/130(57%) were female, 106(82%) black, median age 21(IQR 18-24) years and CD4 count 707(IQR 485-925) cells/μL. L2-4 and/or femur BMD matched for age, sex and ethnicity was abnormal in 13(26%) 15-19 years, 25(50%) 20-24 and 19(63%) 25+. Vitamin D was < 50nmol/l in 42(84%), 36(72%) and 21(70%) with high PTH ( >7.2 pmol/L) in 12(24%), 24(48%) and 11(37%). 85 followed up at a median of 26(IQR 25-28) months; 44(52%) on TAF. Changes in BMD and bone mineral content (BMC) from baseline are shown (Table). There was no difference in BMC delta change with TAF, except for lumbar spine (LS) BMC in 15-19 years (Δ=0.70±0.48 TAF vs 2.18±0.48 non-TAF;p=0.038;all other p >0.25). Predictive factors of LS BMD change were baseline calcium (β=-0.16 per 1 higher;95% -0.32,-0.01;p=0.04); no association was seen with TAF use/duration, age, gender, BMI, mobility, bone markers (NTX, P1NP), PTH, vitamin D or alkaline phosphatase (ALP). LS BMC change was weakly associated with TAF duration (β=+0.04 per month longer;95%CI-0.01, +0.10;p=0.09) and ALP (β=+0.76 per 10 higher;95%CI+0.01,+0.15;p=0.04). In those 20-24 years, greater BMD hip change was associated with PTH (β=-0.01 per 10 higher;-0.02,0.00;p=0.01).
Conclusions:
Reassuringly longitudinal BMD accrual was in keeping with an age, sex and ethnicity-matched population. We found limited evidence of a difference in BMD accrual favouring those receiving TAF-ART compared to non-TAF, non-TDF containing regimens.
Table. Mean and Standard deviation bone mineral density and bone mineral content of YPaHIV at baseline and 26 months, stratified by age group 