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- Title
The Molecular Basis of Nonoxynol-9-Induced Vaginal Inflammation and Its Possible Relevance to Human Immunodeficiency Virus Type 1 Transmission.
- Authors
Fichorova, Raina N.; Tucker, Lynne D.; Anderson, Deborah J.
- Abstract
Topical microbicides are being sought to prevent sexually transmitted diseases by inactivating pathogens while preserving or enhancing the natural mucosal barrier. Serious public health concerns were raised by a recent phase 3 clinical trial that showed that nonoxynol-9 (N-9), a leading microbicide candidate widely used as an over-the-counter spermicide, may actually increase human immunodeficiency virus type 1 (HIV-1) transmission. The present study links N-9-induced vaginal inflammation to increased risk of HIV-1 infection. Analysis of molecular and cellular components in cervicovaginal secretions, as well as results from in vitro activation of cervicovaginal epithelial cells and U1/HIV promonocytic cells, showed that multiple N-9 use can promote HIV-1 transmission through interleukin-1-mediated NF-κB activation, which leads to chemokine-induced recruitment of HIV-1 host cells and increased HIV-1 replication in infected cells. Furthermore, this study identifies in vitro and in vivo model systems for monitoring undesirable proinflammatory effects of microbicides and other vaginal products.
- Subjects
HIV infection transmission; SEXUALLY transmitted diseases
- Publication
Journal of Infectious Diseases, 2001, Vol 184, Issue 4, p418
- ISSN
0022-1899
- Publication type
Article
- DOI
10.1086/322047