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

Amelia E.B. Moore, James E. Burns, Deirdre Sally, Ana Milinkovic, Georgios Krokos, Joemon John, Christopher Rookyard, Alessandro Borca, Erica R.M. Pool, Anna Tostevin, Alyss Harman, Dwight S. Dulnoan, Richard Gilson, Alejandro Arenas-Pinto, Gary J.R. Cook, John Saunders, David Dunn, Glen M. Blake, Sarah L. Pett*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


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, SUVmean) 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-SUVmeandecreased for both groups (TAF -7.9% [95% confidence interval -14.4, -1.5], TDF -5.3% [-12.1,1.5], P = 0.57). TH-SUVmeanshowed 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 (SUVmean) and BMD did not differ postswitch to TAF. However, improved LS-BMD and CTX echo other TAF-switch studies. The lack of difference in SUVmeanmay be due to inadequate power.

Original languageEnglish
Pages (from-to)521-529
Number of pages9
Issue number4
Publication statusPublished - 15 Mar 2024


  • bone density
  • bone turnover
  • HIV
  • PET/computed tomography
  • tenofovir


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