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HIV nucleoside reverse transcriptase inhibitors efavirenz and tenofovir change the growth and differentiation of primary gingival epithelium
Author(s) -
Mitchell D,
Israr M,
Alam S,
Dinello D,
Kishel J,
Jia R,
Meyers C
Publication year - 2014
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1111/hiv.12100
Subject(s) - efavirenz , cytokeratin , reverse transcriptase , proliferating cell nuclear antigen , reverse transcriptase inhibitor , proliferation marker , cell growth , nucleoside reverse transcriptase inhibitor , medicine , immunology , biology , virus , viral load , immunohistochemistry , biochemistry , antiretroviral therapy , rna , gene
Objectives An increasing number of HIV ‐infected patients are combating HIV infection through the use of antiretroviral drugs, including reverse transcriptase inhibitors. Oral complications associated with these drugs are becoming a mounting cause for concern. In our previous studies, both protease inhibitors and reverse transcriptase inhibitors have been shown to change the proliferation and differentiation state of oral tissues. This study examined the effect of a nonnucleoside and a nucleoside reverse transcriptase inhibitor on the growth and differentiation of gingival epithelium. Methods Organotypic (raft) cultures of gingival keratinocytes were treated with a range of efavirenz and tenofovir concentrations. Raft cultures were immunohistochemically analysed to determine the effect of these drugs on the expression of key differentiation and proliferation markers, including cytokeratins and proliferating cell nuclear antigen ( PCNA ). Results These drugs dramatically changed the proliferation and differentiation state of gingival tissues when they were present throughout the growth period of the raft tissue as well as when drugs were added to established tissue on day 8. Treatment with the drugs increased the expression of cytokeratin 10 and PCNA and, conversely, decreased expression of cytokeratin 5, involucrin and cytokeratin 6. Gingival tissue exhibited increased proliferation in the suprabasal layers, increased fragility, and an inability to heal itself. Conclusions Our results suggest that efavirenz and tenofovir treatments, even when applied in low concentrations for short periods of time, deregulated the cell cycle/proliferation and differentiation pathways, resulting in abnormal epithelial repair and proliferation. Our system could be developed as a potential model for studying the effects of HIV and highly active antiretroviral therapy ( HAART ) in vitro .