Discussion
reduced bone loss, proteinuria, weight gain, lower decrease in glomerular filtration, fractures, TAF, TAF-based
We report a comprehensive assessment of bone health in treated PLWHIV after a randomized pilot study with switching from a TDF-based regimen to a TAF-based regimen. In this study individuals who switched to a TAF-based regimen experienced a significant improvement in bone tissue quality measured by bone microindentation at week 24, whereas no changes in bone mineral density were found.Until now, the only way to measure the mechanical resistance of bone was through TDF has been repeatedly associated with its toxic effect on bone. TDF directly interferes with bone homeostasis through the reduction of extracellular adenosine levels, mediated by inhibition of ATP release from cells (Interestingly, we found in a previous study that starting antiretroviral treatment improved bone quality despite the fact that bone mineral density decreased in the first weeks of treatment (In the present study, individuals under TDF regimen at the timepoint of 24 weeks after randomization remained stable regarding bone strength parameters.Tenofovir alafenamide is the tenofovir prodrug. TAF is mostly metabolized intracellularly by cathepsin A to tenofovir, whereas TDF is hydrolyzed by intestine and plasma esterases to tenofovir (TAF-containing regimens showed significantly lower decrease in glomerular filtration rate, less proteinuria and less reduction in BMD in comparison with those receiving TDF-containing regimens. In addition, patients on TDF who switched to TAF had increased BMD (Even though BMD is the gold standard predictor of fragility fractures, incident fractures among HIV individuals are not directly correlated with reduced BMD (All of data suggests that TDF has a larger impact in bone than the PI, INSTI, or NNRTI.In both ART-experienced and ART-naive PLWHIV, INSTI demonstrated better bone safety profile. In a randomized clinical trial, raltegravir was found to be linked with reduced bone loss when taken with TDF/FTC compared to either darunavir/ritonavir (r) or atazanavir/r (Finally, in this study we found a significant association between switch to TAF and weight gain as previously reported due to the lowering weight effect of TDF. However, this increase was associated with an improvement in bone quality (This study has some limitations that must be stated. This is a pilot trial with a reduced sample size in a single center. The reported results must be confirmed in larger studies. However, changes found in this study are physiologically plausible and deserve further studies. Other limitation could be the differences in vitamin D levels between the two timepoints. This could be due to the inclusion took after summer, and the follow up after Winter (24 weeks later) likely reflecting the changes of vitamin D over the year. Despite of that, since this is a randomized study and both arms are balanced in the main variables.One strength of the study is that microindentation is a now plenty available technique that has been recently approved for clinical use and we, as a group, have wide experience with it. The variability between observations is low and the same investigator performed all the measurements.In conclusion, we present a longitudinal randomized switch study where individuals under TDF-based regimen change to TAF and bone tissue quality is assessed. We found that TAF-based group experienced an improvement in bone quality 24 weeks after switching from TDF independently of BMD. Therefore, microindentation is a sensitive tool for detecting early bone changes. Consequently, measuring other keystone elements of bone strength such as bone tissue quality also provides additional information and may more accurately assess bone health status.