[13, 17-19] The spermicide Nonoxynol-9, which was investigated as a potential microbicide to prevent HIV infection, was found to contribute to the development of epithelial lesions.[20] This may explain why women who used Nonoxynol-9 with increased frequency were at higher risk of HIV acquisition.[21]
However, diaphragms or cervical caps have been studied as a means of HIV prevention in women and have failed to demonstrate a protective effect.[22] In this issue of the Journal, Kaushic et al. and Hope et al. describe in further detail the role of the female genital tract epithelial lining in HIV transmission. Animal data using the rhesus macaque model suggest that the cervical mucosa is the first site of HIV infection after vaginal exposure to Simian immunodeficiency virus (SIV), FDA approved Drug Library and HIV-infected cells are not present in the vaginal mucosa until infection has become systemic. Zhang et al.[23] showed that cervical cells were detectably infected with SIV by day 3, whereas the vaginal mucosa was not infected until day 12, coinciding with systemic dissemination. However, there are data from animal models that
do not support the importance of the cervix in acquiring HIV.[24] Unlike the study conducted by Zhang et al. described above, Miller et al.[25] found SIV-infected cells soon after infection both in the cervix and in the stratified squamous epithelium of the vagina. Dendritic cells in the vaginal epithelium are thought to have been important in early HIV uptake in this model. We first JQ1 cell line Palmatine review studies that found
cervical ectopy to be a significant risk factor for HIV acquisition, and then studies that did not find such an association (see Table 1). Moss and colleagues studying 70 HIV-infected men and their female spouses in Nairobi, Kenya found that cervical ectopy was a major predictor of HIV seropositivity (adjusted odds ratio, AOR: 5.0, P = 0.007).[26] Another study conducted among 97 female spouses of HIV-infected men in Nairobi, Kenya found that cervical ectopy was associated with cervical HIV shedding (AOR: 5.0, 95% CI: 1.5–16.9), suggesting its importance in the secondary transmission of HIV.[27] Of note, these women also had concurrently high rates of other STIs, namely N. gonorrhoeae and syphilis. In one of the few analyses to assess HIV incidence, Plourde and colleagues found that among a cohort of 81 Kenyan women with genital ulcers, cervical ectopy increased the risk of acquiring HIV (relative risk, RR: 4.9, 95% CI: 1.5–15.6).[28] However, no women without ulcers were examined so these results could suggest that cervical ectopy is a risk for ulcerative infections or that ulcerative infections of the columnar epithelium make the tissue more vulnerable to HIV.