title: Mucosal effects of tenofovir 1% gel.
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.
authors: Department of Obstetrics and Gynecology, University of Washington, Seattle, United States.
authors: Florian
authors: F
authors: Hladik
authors: Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.
authors: Adam
authors: A
authors: Burgener
authors: Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, United States.
authors: Lamar
authors: L
authors: Ballweber
authors: Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, United States.
authors: Raphael
authors: R
authors: Gottardo
authors: Department of Obstetrics and Gynecology, University of Washington, Seattle, United States.
authors: Lucia
authors: L
authors: Vojtech
authors: Vaccine and Gene Therapy Institute of Florida, Port Saint Lucie, United States.
authors: Slim
authors: S
authors: Fourati
authors: Department of Biostatistics, University of Washington, Seattle, United States.
authors: James Y
authors: JY
authors: Dai
authors: Vaccine and Gene Therapy Institute of Florida, Port Saint Lucie, United States.
authors: Mark J
authors: MJ
authors: Cameron
authors: Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, United States.
authors: Johanna
authors: J
authors: Strobl
authors: Department of Obstetrics and Gynecology, University of Washington, Seattle, United States.
authors: Sean M
authors: SM
authors: Hughes
authors: Department of Medicine, University of Alabama, Birmingham, United States.
authors: Craig
authors: C
authors: Hoesley
authors: FHI 360, Durham, United States.
authors: Philip
authors: P
authors: Andrew
authors: FHI 360, Durham, United States.
authors: Sherri
authors: S
authors: Johnson
authors: Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States.
authors: Jeanna
authors: J
authors: Piper
authors: CONRAD, Eastern Virginia Medical School, Arlington, United States.
authors: David R
authors: DR
authors: Friend
authors: Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.
authors: T Blake
authors: TB
authors: Ball
authors: University of Pittsburgh School of Medicine, Pittsburgh, United States.
authors: Ross D
authors: RD
authors: Cranston
authors: Fenway Health, Beth Israel Deaconess Hospital, Harvard Medical School, Boston, United States.
authors: Kenneth H
authors: KH
authors: Mayer
authors: Department of Medicine, University of Washington, Seattle, United States.
authors: M Juliana
authors: MJ
authors: McElrath
authors: University of Pittsburgh School of Medicine, Pittsburgh, United States.
authors: Ian
authors: I
authors: McGowan
mesh_terms: D004311:Double-Blind Method; D005260:Female; D005782:Gels; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000187:drug effects; D009092:Mucous Membrane / Q000187:drug effects* / Q000378:metabolism; D040901:Proteomics; D012007:Rectum / Q000187:drug effects / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000068698:Tenofovir / Q000008:administration & dosage* / Q000009:adverse effects; D014621:Vagina / Q000187:drug effects / Q000378:metabolism
chemical_list: D005782:Gels; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir
keywords: HIV/AIDS; human; human biology; infectious disease; medicine; microbicides; microbiology; mucosa; prevention; side effects
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