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Improvement in bone quality is observed after switching from the tenofovir disoproxil fumarate regimen to the tenofovir alafenamide regimen of antiretroviral therapy.

People living with HIV (PLWH) are at a higher risk of bone fractures than the general population. As longevity improves with antiretroviral therapy (ART), fracture rates are also predicted to increase in this population. Studies have shown that the tenofovir disoproxil fumarate (TDF) regimen is associated with greater bone mineral density (BMD) loss and increased bone turnover compared to other antiretroviral regimens. Other factors besides BMD, like HIV infection, co-infection, and treatment, also increase the risk of fractures by affecting bone architecture and quality. A study published in the journal Frontiers in Endocrinology explores the effects of switching from TDF to tenofovir alafenamide (TAF)-based ART on bone quality.

Methodology and Study Population

This was a pilot, randomized, 24-week clinical trial comprising 24 PLWH in which 19 subjects were male. The median age at baseline was 43 years. The study population was divided equally into two arms. Patients were continued on the TDF regimen in one arm and shifted to the TAF regimen in the other. No differences were observed in baseline characteristics between the two arms.

Shifting to Tenofovir Alafenamide Improved Bone Quality

After randomization, a significant improvement in the bone material strength index was detected through micro-indentation only in the TAF arm. This result suggests improved bone tissue quality after transitioning to the TAF regimen. In the TDF arm, bone strength parameters remained stable. No significant changes in BMD were observed in either arm.

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Changes in Bone Turnover Markers

The N-terminal propeptide of type-1 collagen, a bone formation marker, was reduced in both arms by the end of the clinical trial. Furthermore, a significant decrease in C-telopeptide, a bone resorption marker, was observed in the TAF arm, indicating reduced bone turnover. No changes were seen in bone alkaline phosphatase in either arm. Furthermore, a positive correlation between weight gain and a switch to TAF was observed, likely attributed to improved bone quality. 

The improvement in bone tissue quality seen in the TAF arm after transitioning from the TDF regimen is an important and clinically consequential finding that can potentially reduce the rate of fragility fractures in PLWH and positively impact their quality of life. Additional studies are needed to validate these findings further. 


Soldado-Folgado, J., Rins-Lozano, O., Arrieta-Aldea, I., Gonzále-Mena, A., Cañas-Ruano, E., Knobel, H., Garcia-Giralt, N., & Güerri-Fernández, R. (2023). Changes in bone quality after switching from a TDF to a TAF based ART: A pilot randomized study. Frontiers in Endocrinology, 14. https://doi.org/10.3389/fendo.2023.1076739