Unveiling the basis of antiretroviral therapy-induced osteopenia: the effects of Dolutegravir, Darunavir and Atazanavir on osteogenesis.

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 three-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, whereas Darunavir exerts no effect.

CONCLUSION

Atazanavir and Dolutegravir impair osteogenesis. It is essential to diagnose impaired osteogenesis early and to devise effective therapeutic interventions to preserve bone health in ART-treated HIV patients, putting it in the context of a correct antiretroviral combination.