Bone mineral density (BMD) improved in the 96 weeks after patients switched from a combination containing tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) as part of the single-tablet regimen elvitegravir/cobicistat/emtricitabine/TAF (E/C/F/TAF, Genvoya). Switching to TAF also resulted in lower levels of parathyroid hormone (PTH) and two bone turnover markers through 48 weeks in this randomized trial.
Because TAF reduces plasma tenofovir levels by 91% compared with TDF, less tenofovir reaches off-target cells. As a result, changing to TAF lowers rates of TDF-associated side effects in clinical trials, including TDF-linked low BMD. U.S. and Canadian collaborators conducted this analysis of a TDF-to-TAF swap study to determine the impact of switching to TAF on spine and hip BMD, PTH (which regulates calcium, phosphorus and vitamin D) and the bone turnover markers bone procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide (CTx).
The trial involved adults taking one of four TDF regimens who were randomized 2:1 to switch to E/C/F/TAF or continue their TDF combination. The four baseline regimens were TDF/emtricitabine (FTC) plus a third agent, elvitegravir/cobicistat/TDF/FTC (Stribild), efavirenz/TDF/FTC (Atripla) and atazanavir/ritonavir plus TDF. Everyone had a viral load below 50 copies/mL for at least 96 weeks with their TDF regimen and an estimated glomerular filtration rate (eGFR) above 50 mL/min.
Of the 1436 trial participants, 959 traded a TDF regimen for E/C/F/TAF and 477 continued their TDF combination. Median age stood at 41 years in the TAF group and 40 years in the TDF group; 11% in both groups were women, and around 67% in both groups were white. Median eGFR stood at 106 mL/min in the TAF group and 108 mL/min in the TDF group.
Compared with maintaining any TDF regimen, switching to E/C/F/TAF resulted in more than 2% higher spine BMD between weeks 48 and 96 and in more than 2.6% higher hip BMD at week 96 (P < .001 for both comparisons). Median PTH rose significantly through 96 weeks with each of the continued TDF regimens compared with stable PTH levels in people switching to E/C/F/TAF. CTx rose with continued TDF combinations while usually dropping with E/C/F/TAF. P1NP fell significantly after the switch to E/C/F/TAF while remaining stable in people who continued a TDF regimen.
The researchers propose that switching from TDF to TAF "may be associated with reduced risk of osteoporosis and fragility fracture over the long term."