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HIV protease inhibitors block oral epithelial cell DNA synthesis

Robert J Danaher1, Chunmei Wang, Andrew T Roland

  • 1Department of Oral Health Practice, University of Kentucky, Lexington, KY 40536-0297, USA.

Archives of Oral Biology
|December 29, 2009
PubMed
Abstract

Insights

Certain HIV protease inhibitors (PIs) reduce oral epithelial cell proliferation by inhibiting DNA synthesis. This finding may explain adverse oral health effects associated with PI therapy.

Area of Science:

  • Cell Biology
  • Pharmacology
  • Oral Health

Background:

  • Anti-retroviral therapy (ART) regimens containing HIV protease inhibitors (PIs) are linked to adverse effects like oral warts and gastrointestinal issues.
  • These side effects suggest PIs may impact epithelial cell biology, particularly in the oral cavity.

Purpose of the Study:

  • To investigate the effects of PIs on the biological processes of oral epithelium.
  • To determine if PIs perturb oral epithelial cell function.

Main Methods:

  • Oral keratinocytes and squamous carcinoma cells were cultured with pharmacologically relevant concentrations of PIs.
  • Cell viability, cytotoxicity, and DNA synthesis were assessed using enzymatic assays and BrdU incorporation.

Main Results:

  • Select PIs significantly reduced the viability of oral epithelial cells at plasma-relevant concentrations.
  • Nelfinavir was the most potent inhibitor, followed by lopinavir and saquinavir.
  • Reduced viability was attributed to the inhibition of DNA synthesis, not cytotoxicity.

Conclusions:

  • Certain PIs inhibit oral epithelial cell proliferation in a drug- and dose-dependent manner by blocking DNA synthesis.
  • This mechanism may explain some of the adverse oral health effects observed in patients on PI-based ART.

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