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

AIDS. 2021 Feb 2;35(2):213-218. doi: 10.1097/QAD.0000000000002732.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents* / adverse effects
  • Atazanavir Sulfate / adverse effects*
  • Atazanavir Sulfate / therapeutic use
  • Bone Diseases, Metabolic* / chemically induced
  • Darunavir / adverse effects*
  • Darunavir / therapeutic use
  • HIV Infections* / complications
  • HIV Infections* / drug therapy
  • Heterocyclic Compounds, 3-Ring / adverse effects*
  • Heterocyclic Compounds, 3-Ring / therapeutic use
  • Humans
  • Osteogenesis
  • Oxazines / adverse effects*
  • Oxazines / therapeutic use
  • Piperazines / adverse effects*
  • Piperazines / therapeutic use
  • Pyridones / adverse effects*
  • Pyridones / therapeutic use

Substances

  • Anti-HIV Agents
  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Pyridones
  • Atazanavir Sulfate
  • dolutegravir
  • Darunavir