Mucosal effects of tenofovir 1% gel
- University of Washington, United States
- University of Manitoba, Canada
- Fred Hutchinson Cancer Research Center, United States
- Vaccine and Gene Therapy Institute of Florida, United States
- Univeristy of Washington, United States
- University of Alabama, United States
- FHI 360, United States
- National Institutes of Health, United States
- Eastern Virginia Medical School, United States
- University of Pittsburgh School of Medicine, United States
- Beth Israel Deaconess Hospital, Harvard Medical School, United States
- Univeristy of Pittsburgh School of Medicine, United States
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.
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Human subjects: MTN-007 (ClinicalTrials.gov registration NCT01232803) was a phase 1, double blind, placebo-controlled trial in which participants were randomized to receive rectal reduced glycerin tenofovir 1%, nonoxynol-9 (N-9) 2% or hydroxyethylcellulose (HEC) gels, or no-treatment (1:1:1:1), at three clinical research sites (Pittsburgh, PA; Birmingham, AL; and Boston, MA). The study protocol was approved by IRBs at all three sites. All participants gave written informed consent. The study details, and general safety and acceptability data, have been published elsewhere (McGowan I et al. [2013] A phase 1 randomized, double blind, placebo controlled rectal safety and acceptability study of tenofovir 1% gel [MTN-007]. PLoS ONE 8: e60147). CONSORT checklist, CONSORT flow chart and MTN-007 IRB approval were submitted with the prior paper, and are attached again here.
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This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Mucosal effects of tenofovir 1% gel
eLife 4:e04525.
https://doi.org/10.7554/eLife.04525
