PrEP: Bone Density Improves after Stopping TDF/FTC

Tenofovir disoproxil fumarate (TDF) may cause decreases in bone mineral density (BMD) both in HIV-infected patients treated with TDF-containing ARV regimens and in HIV-uninfected persons who use it for PrEP. A substudy of the large iPrEx trial of TDF/FTC PrEP in MSM and transgender womenevaluated the reversibility of BMD changes after discontinuation of PrEP. Researchers took serial BMD measurements (via DEXA scan) in 498 subjects before, during, and after discontinuation of PrEP, and then stratified their analyses according to levels of tenofovir diphosphate in peripheral blood mononuclear cells (PBMCs) (obtained after 6 months on PrEP) and age of the subjects.

In the group with PBMC tenofovir concentrations that correlated with use of at least 2-3 tablets per week, hip BMD decreased by approximately 1% and spine BMD decreased by approximately 2% by the time of stopping PrEP (after a median of 1.5 years on PrEP). BMD did not decrease significantly in the placebo group or the group with low tenofovir concentrations. Bone density reaccumulated after discontinuation of PrEP. In subjects who were <25 years of age, BMD returned to baseline within 6 months after stopping PrEP; in those ≥25 years of age, spine BMD recovered to baseline by 6 months after stopping PrEP, and hip BMD returned to baseline by a median 1.5 years after stopping TDF/FTC. Full recovery of BMD also was noted in subjects whose tenofovir levels correlated with the use of at least 4 tablets of TDF/FTC per week.

Clinical Bottom Line

The bone effects of TDF/FTC PrEP are of concern, especially because of its potential use in young individuals (who may benefit from PrEP) at a time when accrual of bone mass is particularly important. This study provides reassurance that BMD recovery is possible and perhaps likely after discontinuation of TDF/FTC, but data on the effects of longer duration of PrEP use, of cycling on and off PrEP, and of PrEP in other populations (such as women and older persons) are needed and hopefully will be forthcoming.


Grant R, Mulligan K, McMahan, et al; iPrEx Study Team. Recovery of bone mineral density after stopping oral HIV preexposure prophylaxis. In: Program and abstracts of the 2016 Conference on Retroviruses and Opportunistic Infections; February 22-25, 2016; Boston. Abstract 48LB.

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