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J Infect Dis. 2001 Aug 15;184(4):418-28. Epub 2001 Jul 16.

The molecular basis of nonoxynol-9-induced vaginal inflammation and its possible relevance to human immunodeficiency virus type 1 transmission.

Author information

1
Fearing Research Laboratory, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Thorn-217, Boston, MA 02115, USA. rfichorova@rics.bwh.harvard.edu

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-kappaB 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.

PMID:
11471099
DOI:
10.1086/322047
[Indexed for MEDLINE]

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