Abstract Body

Switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) may represent an important treatment strategy to improve bone health in HIV-infected individuals with low bone mineral density (BMD), but this has not been specifically investigated.

This analysis consisted of pooled data from two prospective Phase 3 studies (Studies 109 and 112) of HIV suppressed adults on a TDF-based regimen switching to elvitegravir, cobicistat, and emtricitabine (E/C/F) co-formulated with TAF. In adults with clinically significant low BMD by dual energy x-ray absorptiometry (T-score ≤ -2.0 at the lumbar spine, femoral neck, or total hip) at baseline (BL), we assessed percentage change in BMD and T-score at the lumbar spine and total hip and change in proportion with osteoporosis (T-score ≤ -2.5 at any site) at Weeks (W) 96. Logistic regression was used to determine BL predictors of a clinically significant improvement (≥ 5% increase) in lumbar spine and total hip BMD, adjusted for age, race, sex, and BL BMD.

Of the 1117 enrolled who switched from TDF to TAF, 214 (19%) had clinically significant low BMD at BL (median age 46 years, 85% male, 63% White, 26% smokers) with 43% (93/214) osteoporosis. The BL median (interquartile range: Q1, Q3) T-score (lowest of any 3 sites) was -2.4 (-2.8, -2.2). At the spine, the median (Q1, Q3) % BMD change at W96 was 2.53% (0.22%, 5.31%) and T-score change was 0.19 (0.02, 0.42) (all p<0.001). At total hip, BMD change at W96 was 2.39% (0.72%, 4.18%) and T-score change was 0.14 (0.04, 0.24) (all p<0.001). Of the 86 with BL osteoporosis and W96 BMD data, 23% no longer met criteria for osteoporosis at W96. Of 214 with low BMD, 24% and 15% had a clinically significant BMD increase at the spine and total hip, respectively. In multivariable analysis, BL factors associated with clinically significant BMD increase at W96 were higher fraction excretion of phosphate (FEPO4 ≥ 10%) for the hip and higher BMI (≥30 kg/m2) and procollagen type 1 N-terminal propeptide (P1NP >1.85 log10 ng/mL) levels for spine.

HIV-infected individuals with clinically significant low BMD on a TDF-based regimen who switched to E/C/F/TAF experience a ~2.5% BMD increase over 96 weeks and a reversion from osteoporosis in approximately 1/4 of patients. Baseline urinary phosphate wasting and high bone turnover may identify TDF-treated HIV-infected patients with low BMD who may benefit the most from a switch to TAF.