Bone turnover change after randomized switch from tenofovir disoproxil to tenofovir alafenamide fumarate in men with HIV

Objective:Bone loss in people with HIV (PWH) is poorly understood. Switching tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) has yielded bone mineral density (BMD) increases. PETRAM (NCT#:03405012) investigated whether BMD and bone turnover changes correlate.Design:Open-label, randomized controlled trial.Setting:Single-site, outpatient, secondary care.Participants:Nonosteoporotic, virologically suppressed, cis-male PWH taking TDF/emtricitabine (FTC)/rilpivirine (RPV) for more than 24 weeks.Intervention:Continuing TDF/FTC/RPV versus switching to TAF/FTC/RPV (1 : 1 randomization).Main outcome measures::[¹⁸F]NaF-PET/CT for bone turnover (standardized uptake values, SUV_mean) and dual-energy x-ray absorptiometry for lumbar spine and total hip BMD.Results:Thirty-two men, median age 51 years, 76% white, median duration TDF/FTC/RPV 49 months, were randomized between 31 August 2018 and 09 March 2020. Sixteen TAF:11 TDF were analyzed. Baseline-final scan range was 23-103 (median 55) weeks. LS-SUV_meandecreased for both groups (TAF -7.9% [95% confidence interval -14.4, -1.5], TDF -5.3% [-12.1,1.5], P = 0.57). TH-SUV_meanshowed minimal changes (TAF +0.3% [-12.2,12.8], TDF +2.9% [-11.1,16.9], P = 0.77). LS-BMD changes were slightly more favorable with TAF but failed to reach significance (TAF +1.7% [0.3,3.1], TDF -0.3 [-1.8,1.2], P = 0.06). Bone turnover markers decreased more with TAF ([CTX -35.3% [-45.7, -24.9], P1NP -17.6% [-26.2, -8.5]) than TDF (-11.6% [-28.8, +5.6] and -6.9% [-19.2, +5.4] respectively); statistical significance was only observed for CTX (P = 0.02, P1NP, P = 0.17).Conclusion:Contrary to our hypothesis, lumbar spine and total hip regional bone formation (SUV_mean) and BMD did not differ postswitch to TAF. However, improved LS-BMD and CTX echo other TAF-switch studies. The lack of difference in SUV_meanmay be due to inadequate power.