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

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.

• Authors: Alessandra Cazzaniga, Roberta Scrimieri, Massimo Galli, Jeanette Maier, Stefano Rusconi
• Journal: AIDS (London, England) (AIDS) Vol. 35 Issue 2 Pg. 213-218 (02 02 2021) ISSN: 1473-5571 [Electronic] England
• PMID: 33394669 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Chemical References

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

Topics

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