The hypothesis that diaphragms might offer women some protection against sexually transmitted infections (STIs), including HIV, will soon be tested in several randomized controlled trials.
One study of the use of diaphragms to prevent transmission of bacterial STIs, funded by the U.S.-based CONRAD Program, is under way in Nairobi, Kenya.1 Results are expected in about four years. The U.S.-based Population Council plans to begin a similar study involving about 400 sex workers in the Dominican Republic later in 2003. Meanwhile, the first randomized controlled trial of the diaphragm's protective effect against HIV is expected to begin in Zimbabwe, South Africa, and one other country in mid-2003. That trial will be conducted by researchers at the University of California at San Francisco (UCSF), USA, with results expected in three or four years.
Testing the diaphragm's effectiveness against bacterial STIs was logical because gonorrhea and chlamydial infection are clearly acquired in the cervix and not the vagina. And evidence of the diaphragm's potential to protect against these and other STIs has been accumulating.2
If the diaphragm does indeed protect the cervix against STIs, it might indirectly protect against HIV, since HIV infection is facilitated by the presence of other STIs. Meanwhile, "it looks as though the majority of HIV infections probably occur at the cervix, which is more vulnerable than the vagina," says Dr. Nancy Padian, a professor of obstetrics, gynecology, and reproductive sciences at UCSF and principal investigator for the randomized trial.
One reason for this greater susceptibility is that the endocervical lining is thinner and more fragile than the lining of the vagina. It is particularly vulnerable when it extends out onto the face of the cervix, a condition known as cervical ectopy that is common in adolescents.3 The cervix also seems to be the primary site for a number of HIV receptors, which are proteins on cell surfaces that facilitate attachment and entry of the virus into those cells.4
Most studies using animal models of HIV infection have found that the cervix is usually infected first, Dr. Padian notes. When rhesus macaque monkeys were injected with the HIV-like simian immunodeficiency virus (SIV), cervical cells were infected after three days, while vaginal cells were not infected until the twelfth day.5 There is, however, some conflicting evidence.6 Another study in macaques found SIV-infected cells in both the vagina and the cervix soon after infection, and in one study removal of the cervix in macaques did not decrease the efficiency of SIV transmission.7 Moreover, women who have had hysterectomies have acquired HIV infection vaginally.8
Diaphragms alone are unlikely to provide 100 percent protection against HIV because transmission can occur vaginally, particularly — but not exclusively — when the epithelial cells on the surface of the vagina are disrupted.9 "If there is any physical microtrauma or any inflammatory alteration of the vaginal epithelium, then transmission can very readily take place," says Dr. Robin Shattock, senior lecturer in the Department of Infectious Diseases at St. George's Medical School in London, UK, who has conducted research on the mechanisms of HIV transmission to women. "There's no way to tell what degree of protection diaphragms will provide without conducting trials."
Diaphragms and microbicides
Some researchers think that dia-phragms and microbicides may be most effective if used together. Coated on both sides with a microbicide, a diaphragm could block STI pathogens from the cervix and help improve retention of the microbicide in both the cervix and the vagina. To explore the impact of combined use of these methods on STI acquisition, principal investigators for the Kenyan diaphragm and STI study — Dr. Craig Cohen of the University of Washington, USA, and Dr. Elizabeth Bukusi of the Centre for Microbiology Research at the Kenya Medical Research Institute — are adding two arms to the trial: one consisting of women who use diaphragms and a microbicide, and one with women who use only a microbicide.
Recognizing that effectiveness will also depend on consistent use, researchers are examining the acceptability of dia-phragms among women in Brazil, Kenya, and Zimbabwe. Diaphragms are not a popular contraceptive method now, but that may change if they prove to provide protection against HIV and other STIs. "There is a lot of feeling out there that women will not use a barrier method consistently for a long time," says Marianne Callahan, clinical director at CONRAD, which is designing studies that will ask women in South Africa and Zimbabwe to use diaphragms alone or diaphragms with a microbicide. "We would like to show that they will, if they are given a good reason."
— Kathleen Henry Shears
References
Cohen C. The diaphragm: a female controlled method to prevent HIV and other sexually transmitted infections? Microbicides 2002, Antwerp, Belgium, May 12-15, 2002.
Moench TR, Chipato T, Padian NS. Preventing disease by protecting the cervix: the unexplored promise of internal vaginal barrier devices. AIDS 2001;15(13):1595-1602.
Moench.
Moench; Levine WC, Pope V, Ghoomkar A, et al. Increase in endocervical CD4 lymphocytes among women with nonulcerative sexually transmitted disease. J Infect Dis 1998;177(1):167-74; Zhang L, He T, Talal A, et al. In vivo distribution of the human immuno-deficiency virus/simian immunodeficiency virus coreceptors: CSCR4, CCR3, and CCR5. J Virol 1998;72(6):5035-45.
Zhang Z-Q, Schuler T, Zupacic M, et al. Sexual transmission and propagation of SIV and HIV in resting and activated CD4+ cells. Science 1999;286(5443):1353-57.
Moench; Mingjia M, Short R. How oestrogen or progesterone might change a woman's susceptibility to HIV-1 infection. Aust NZ J Ob Gyn 2002;42(5):472-75.
Miller CJ. Mucosal transmission of simian immunodeficiency virus. Curr Top Microbiol Immunol 1994;188:107-22; Hu J, Gardner MB, Miller CJ. Simian immunodeficiency virus rapidly penetrates the cervicovaginal mucosa after intravaginal inoculation and infects intraepithelial dendritic cells. J Virol 2000;74(13):6087-95.
Goedert JJ, Eyster ME, Biggar RJ, et al. Heterosexual transmission of human immuno-deficiency virus: association with severe depletion of T-helper lymphocytes in men with hemo-philia. AIDS Res Hum Retrovir 1987;3(4):355-61.
Miller CJ, Shattock RJ. Target cells in vaginal HIV transmission. Microbes and Infection 2003;5(1):59-67.
The Today contraceptive vaginal sponge has just re-entered the market on a limited basis after an eight-year hiatus. Currently available only in Canada, the sponge is an alternative to the diaphragm that can be obtained without a prescription and used for multiple acts of intercourse within a 24-hour period.
The sponge protects against pregnancy by blocking sperm from entering the cervix and by releasing the spermicide nonoxynol-9. (Notably, potential users of the sponge should be aware that nonoxynol-9 has been shown to increase the risk of HIV infection when used frequently by women at high risk of infection [see N-9 Not for Women at High Risk of HIV Infection]). A recent Cochrane Review conducted by FHI shows pregnancy rates during one year of use to be 17 percent to 24 percent for the sponge compared with 11 percent to 13 percent for the diaphragm.1 With support from the U.S. Agency for International Development (USAID) and the National Institutes of Health, FHI also conducted the clinical trials that led to the U.S. Food and Drug Administration's (FDA's) original approval of the sponge in 1983. The sponge's original manufacturer took the product off the market in 1995 after problems that would have required a costly upgrade were found at the manufacturing plant. The current manufacturer — New Jersey-based Allendale Pharmaceuticals — must gain a second FDA approval before the sponge can be sold again in the United States. To read more, click here.
— Kerry L. Wright
Reference
Kuyoh MA, Toroitich-Ruto C, Grimes DA, et al. Sponge versus diaphragm for contraception: a Cochrane review. Contraception 2003;67(1):15-18.
