Objectives: Osteopenia is frequent in HIV infected patients treated with antiretroviral therapy (ART) and has been linked to increased osteoclastogenesis. Little is known about the effects of ART on osteogenesis. Design: We investigated the effect on human mesenchymal stem cells (hMSC) and osteoblasts of Darunavir and Dolutegravir, the most highly used as anchor drugs within a 3-drug regimen, and Atazanavir, which was widely utilized in the past. Results: We found that Atazanavir and Dolutegravir delay the osteogenic differentiation of hMSC, impair the activity of osteoblasts and inhibit their conversion into osteocytes, while Darunavir exerts no effect. Conclusions: Atazanavir and Dolutegravir impair osteogenesis. It is essential to early diagnose impaired osteogenesis and to devise effective therapeutic interventions to preserve bone health in ART-treated HIV patients and put it in the context of a correct antiretroviral combination.

Unveiling the basis of ART-induced osteopenia / A. Cazzaniga, R. Scrimieri, M. Galli, J. Maier, S. Rusconi. - In: AIDS. - ISSN 0269-9370. - (2020). [Epub ahead of print] [10.1097/QAD.0000000000002732]

Unveiling the basis of ART-induced osteopenia

A. Cazzaniga
Primo
;
R. Scrimieri
Secondo
;
M. Galli;J. Maier
Penultimo
;
S. Rusconi
Ultimo
2020

Abstract

Objectives: Osteopenia is frequent in HIV infected patients treated with antiretroviral therapy (ART) and has been linked to increased osteoclastogenesis. Little is known about the effects of ART on osteogenesis. Design: We investigated the effect on human mesenchymal stem cells (hMSC) and osteoblasts of Darunavir and Dolutegravir, the most highly used as anchor drugs within a 3-drug regimen, and Atazanavir, which was widely utilized in the past. Results: We found that Atazanavir and Dolutegravir delay the osteogenic differentiation of hMSC, impair the activity of osteoblasts and inhibit their conversion into osteocytes, while Darunavir exerts no effect. Conclusions: Atazanavir and Dolutegravir impair osteogenesis. It is essential to early diagnose impaired osteogenesis and to devise effective therapeutic interventions to preserve bone health in ART-treated HIV patients and put it in the context of a correct antiretroviral combination.
antiretroviral therapy; INSTIs; PIs; mesenchymal stem cell; osteoblast, osteogenesis
Settore MED/17 - Malattie Infettive
Settore MED/04 - Patologia Generale
2020
ott-2020
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/788909
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