Preventing HIV/STIs

Why is research on cervical barriers important?

• The HIV pandemic is affecting women and girls in increasing numbers. In sub-Saharan Africa, where nearly two-thirds of HIV-infected people live, women are more than 1.3 times more likely to be infected than men. Young women between the ages of 15 and 24 are three times more likely to be infected than young men in this age group and make up approximately three-quarters of young people who are HIV-positive in sub-Saharan Africa. In Russia and Asia, where HIV rates are escalating, a third of all new infections are among women. In the United States, women are likely to constitute half of all new HIV infections by 2010.
• Women are biologically more vulnerable to infection and its consequences, and are at least twice as likely as men to contract HIV from unprotected intercourse.
• Gender inequities prevent many women from being able to protect themselves from infection. Violence, coercion, and economic dependency render millions of women unable to negotiate condom use or to abandon partners who put them at risk.

Overview

The renewed interest in cervical barrier methods resulted in part from new evidence about the role that the cervix may play in HIV/STI transmission. To date, condom use is the only method proven to reduce the risk of HIV/STI infection through sex; however, negotiating condom use remains difficult for some people, and scientists are researching potential alternatives to increase prevention options, particularly for women.

This section presents the relevant information on cervical barriers as potential HIV/STI prevention methods, detailing the biological vulnerability of the cervix and providing information on evidence and research and references on this topic.

Biological vulnerability of the cervix

The cervix is the lower opening of the uterus and the gateway to the uterus and the rest of the upper genital tract. It is compromised of three main areas: the endocervix, the transformation zone, and the ectocervix. The vagina and ectocervix, or outer edge of the cervix, are lined with approximately 30 layers of tough squamous cells. In contrast, the endocervix, or the area inside and around the opening to the uterus, is covered with one layer of delicate, columnar epithelial cells. The transformation zone is the area between the ectocervix and endocervix where columnar epithelial cells are replaced by squamous epithelial cells, thus enlarging the ectocervix. This transformation happens rapidly during puberty.

The columnar epithelial cells of the endocervix appear to be particularly vulnerable to sexually transmitted infections (STIs); chlamydial and gonococcal infections are most commonly seen in the cells of the endocervix. The transformation zone is the region most vulnerable to dysplasia (precancerous changes), and new research seems to indicate that receptors for HIV are concentrated there as well. In fact, researchers believe the cervix may be the primary site of HIV infection in women.

Click for larger diagram

At the Diaphragm Renaissance meeting in September 2002, virologist Jay Levy and immunologists Dr. Deborah Anderson and Dr. Charles Wira reported on current knowledge of the pathways of HIV infection in women. Their research findings implicate the uterus, and thus the cervix, as sites that are particularly vulnerable to HIV infection, largely because many of the receptors known to facilitate HIV transmission (including CCR5 and CXCR4) are concentrated on the cervix.

Since HIV can infect women who have had hysterectomies, the cervix cannot be the only site of infection in women. Drs. Anderson and Wira showed that there are HIV receptors in the vagina, and much evidence shows that STIs may cause symptoms (such as sores or lesions) that compromise the vaginal walls and make these areas more vulnerable to HIV infection. Clearly, covering the cervix would likely only provide partial protection from HIV and other STIs. Drs Anderson and Wira also showed a number of receptor sites in the upper genital tract (uterine endometrium, fallopian tubes, and ovaries), and covering the cervix could also protect these vulnerable areas. Researchers are currently evaluating whether the diaphragm could provide protection against HIV and other STIs in clinical trials.

Evidence and research

Although to date there have been no experimental studies (i.e., controlled trials) to evaluate the effect of diaphragm use on HIV/STI acquisition, there have been several observational studies (case-control or cross sectional designs) that report that using the diaphragm is associate with a reduced risk of STIs and associated long-term sequelae. All of the studies compared diaphragm users to nonusers, and all used some type of multivariate analysis to control for known co-factors or confounders such as socioeconomic status or age. Although not always specified, in most studies women who used diaphragms did so together with spermicides. Thus, although we cannot separate the protective effect of diaphragms from that of spermicides used alone, this limitation does not affect our fundamental argument that diaphragms used together with microbicides may offer significant protection. The table below (adapted from Moench, Chipato, and Padian, 2001) summarizes these results. Because the majority of these studies were not designed to test the efficacy of the diaphragm as their primary objective, and because they are all observational studies and thus subject to biases, results in the table must be seen as suggestive rather than definitive.

Click for larger diagram

To date, no studies have examined the protective effect of physical coverage of the cervix and HIV acquisition. However, because of its fragility, frequent compromise by classical STIs, and the presence of HIV-receptor sites (all of which are discussed above), the cervix is likely more susceptible to HIV than vaginal tissue. The data reported here are observational, and the use of cervical barriers for HIV/STI prevention cannot be recommended based on this data, but more research is now underway.

References

Austin H, Louv WC, Alexander WJ: A case-control study of spermicides and gonorrhea. JAMA 1984, 251:2822-4.

Becker TM, Wheeler CM, McGough NS, Stidley CA, Parmenter CA, Dorin MH, Jordan SW: Contraceptive and reproductive risks for cervical dysplasia in southwestern Hispanic and non-Hispanic white women. Int J Epidemiol 1994, 23:913-22.

Kelaghan J, Rubin GL, Ory HW, Layde PM: Barrier-method contraceptives and pelvic inflammatory disease. JAMA 1982, 248:184-187.

Magder LS, Harrison HR, Ehret JM, Anderson TS, Judson FN: Factors related to genital chlamydia trachomatis and its diagnosis by culture in a sexually transmitted disease clinic. Am J Epidemiol 1988, 128:298-308.

Moench T, Chipato T, Padian N. Preventing disease by protecting the cervix: the unexplored promise of internal vaginal barrier devices. AIDS 2001;15:1595-1602.

Rosenberg MJ, Davidson AJ, Chen JH, Judson FN, Douglas JM: Barrier contraceptives and sexually transmitted diseases in women: a comparison of female-dependent methods and condoms. Am J Public Health 1992, 82:669-74.

Wolner-Hanssen P, Eschenbach DA, Paavonen J, et al: Decreased risk of symptomatic chlamydial pelvic inflammatory disease associated with oral contraceptive use. JAMA 1990, 263:54-59.