Mucosal effects of tenofovir 1% gel
Florian Hladik, Adam Burgener, Lamar Ballweber, Raphael Gottardo, Lucia Vojtech, Slim Fourati, James Y Dai, Mark J Cameron, Johanna Strobl, Sean M Hughes, Craig Hoesley, Philip Andrew, Sherri Johnson, Jeanna Piper, David R Friend, T Blake Ball, Ross D Cranston, Kenneth H Mayer, M Juliana McElrath, Ian McGowan, Florian Hladik, Adam Burgener, Lamar Ballweber, Raphael Gottardo, Lucia Vojtech, Slim Fourati, James Y Dai, Mark J Cameron, Johanna Strobl, Sean M Hughes, Craig Hoesley, Philip Andrew, Sherri Johnson, Jeanna Piper, David R Friend, T Blake Ball, Ross D Cranston, Kenneth H Mayer, M Juliana McElrath, Ian McGowan
Abstract
Tenofovir gel is being evaluated for vaginal and rectal pre-exposure prophylaxis against HIV transmission. Because this is a new prevention strategy, we broadly assessed its effects on the mucosa. In MTN-007, a phase-1, randomized, double-blinded rectal microbicide trial, we used systems genomics/proteomics to determine the effect of tenofovir 1% gel, nonoxynol-9 2% gel, placebo gel or no treatment on rectal biopsies (15 subjects/arm). We also treated primary vaginal epithelial cells from four healthy women with tenofovir in vitro. After seven days of administration, tenofovir 1% gel had broad-ranging effects on the rectal mucosa, which were more pronounced than, but different from, those of the detergent nonoxynol-9. Tenofovir suppressed anti-inflammatory mediators, increased T cell densities, caused mitochondrial dysfunction, altered regulatory pathways of cell differentiation and survival, and stimulated epithelial cell proliferation. The breadth of mucosal changes induced by tenofovir indicates that its safety over longer-term topical use should be carefully monitored.
Keywords: HIV/AIDS; human; human biology; infectious disease; medicine; microbicides; microbiology; mucosa; prevention; side effects.
Conflict of interest statement
The authors declare that no competing interests exist.
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References
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