| Autor: |
Hladik F; Department of Obstetrics and Gynecology, University of Washington, Seattle, United States., Burgener A; Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada., Ballweber L; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, United States., Gottardo R; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, United States., Vojtech L; Department of Obstetrics and Gynecology, University of Washington, Seattle, United States., Fourati S; Vaccine and Gene Therapy Institute of Florida, Port Saint Lucie, United States., Dai JY; Department of Biostatistics, University of Washington, Seattle, United States., Cameron MJ; Vaccine and Gene Therapy Institute of Florida, Port Saint Lucie, United States., Strobl J; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, United States., Hughes SM; Department of Obstetrics and Gynecology, University of Washington, Seattle, United States., Hoesley C; Department of Medicine, University of Alabama, Birmingham, United States., Andrew P; FHI 360, Durham, United States., Johnson S; FHI 360, Durham, United States., Piper J; Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States., Friend DR; CONRAD, Eastern Virginia Medical School, Arlington, United States., Ball TB; Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada., Cranston RD; University of Pittsburgh School of Medicine, Pittsburgh, United States., Mayer KH; Fenway Health, Beth Israel Deaconess Hospital, Harvard Medical School, Boston, United States., McElrath MJ; Department of Medicine, University of Washington, Seattle, United States., McGowan I; University of Pittsburgh School of Medicine, Pittsburgh, United States. |
| Abstrakt: |
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. |
