Woman-Initiated Methods for HIV Prevention
Avoiding sexually transmitted diseases (STDs), including HIV, can be more complicated for women than for men. The circumstances under which women have sexual encounters with partners vary both with their own demographic background (age, culture, religion, socioeconomic status, sexual preference, etc.) and also with the particular partnership. Characteristics such as male or female partner(s); casual or long-term relationships; exchange of sex for money, drugs or shelter; dominant, submissive or egalitarian roles; desire to have children; and use of contraceptive methods all affect decisions about protections against STDs. Condoms provide good protection from HIV and other STDs when used properly and consistently during vaginal and anal intercourse. But women rarely learn how to initiate use of condoms, and must generally rely upon partner cooperation. Abstinence is not always an option, as nonconsensual or unplanned sexual intercourse is a common reality.
The focus in research at present is to develop woman-initiated methods. Educators teach communication and dialogue skills, rather than assuming that argument and conflict with a sexual partner is inevitable. Teaching a universal message ("condoms are the only safe option") is replaced with a hierarchical model of choosing what is best among several options.
Technical products for safer sex are referred to as "barriers." Women need to know the nature of each type of barrier, its relative effectiveness and availability, and how to acquire experience in its use. Mechanical barriers (male and female condom, diaphragm, cervical cap) and chemical barriers (bacteria- and virus-killing microbicides) can be used alone or in combination.
Condoms: The male condom, usually made of latex, protects the penis completely, if correctly and consistently used. But it is usually (though not always) applied by the man, and he does so after achieving an erection, which is sometimes preceded by the escape of potentially pathogen-bearing semen. Condoms also slip and break. Protection cannot be 100% effective against infections, nor has it proven so against conception. Nevertheless, condoms have been shown in many careful studies to greatly reduce the chances for men and for women of acquiring sexually transmitted diseases, including HIV.
Male condoms are cheap and widely available. Their chief drawback for women is the uncertainty as to whether their partner will agree to use them. A woman may buy a man's condom (although not without possible embarrassment), but she will still have to negotiate with a male partner over its use. And, of course, there's the rub. Commercial sex workers working in licensed brothels in Nevada, for example, extract almost complete "compliance" from their clients. The record is far poorer in almost all other surveyed partnerships in the U.S. and elsewhere.
The female condom, although far less familiar and much less tested both against infections and conception, provides a physical barrier to the vulva as well as to the vagina and cervix, and to the penis. It is made of a durable material, polyurethane, that is probably less likely to slip or break than the latex male condom. Because it may be applied well before intercourse, there is no question of infection from pre-erection discharge. The woman's condom definitely assigns the initiative to the woman, and in almost all cases, women report a feeling of empowerment in being permitted this initiative. Nevertheless, in using this device, the man must give at least passive assent. For both women and men, comfort increases with experience.
The woman's condom is more expensive than the man's condom, and is not always available. Recent (still unpublished) reports suggest that it is as effective against unwanted conception as is the male condom; preliminary findings also report favorable results against infections.
Attempts to compare the protection conferred by the male and female condoms have to consider both method efficacy (how well the method protects when used correctly) and overall effectiveness (the reduction in infections that occur when the method is made available to the population). Although almost impossible to test scientifically, it is likely that both condoms would score equally high on method efficacy. Overall effectiveness depends on usage, which depends in turn on concerted efforts to promote a given method. With the woman's condom, studies have shown reasonable uptake on short follow-ups, but there is a dearth of long follow-ups.
A major limitation to wider use of the female condom is its price ($8.49 for three). A topic under active study is whether the female condom could be safely reused. If procedures to do so were established and permitted by the FDA, the cost to a woman or public agency could be greatly reduced.
Diaphragm, Cervical Cap: These are the best established devices that provide some protection to the cervix, especially when used with chemical barriers, which are discussed below.
The diaphragm has a long history as a contraceptive, with effectiveness for that purpose similar to the male condom. Its great appeal for women is that it can be used clandestinely; that is, a male sexual partner does not have to know it is being used. The diaphragm has to be fitted by a physician or qualified health worker, but a woman can keep using the same one for years, although it is advisable to be refitted after giving birth. There is some ongoing research to make a "one size fits all" diaphragm so as to obviate the fitting visit, but at this time the device remains essentially as it was 70 years ago. With the advent of the contraceptive pill, its use declined markedly.
The cervical cap also covers the cervix. It has certain advantages over the diaphragm, for example it can be left in place for longer periods of time and for several sexual encounters. But cervical caps also must be fitted and there are fewer providers who have experience doing so.
The main disadvantage of these devices, and why they must be ranked below the condoms, is that they are very likely less effective against HIV. This is because they cover only the cervix and according to a recently published study there is a potential for HIV infection to take place at any level of the reproductive tract, including the uterus and vagina (Howell AL et al. Journal of Virology. May 1997; 71(5):3498-506).
Basic and clinical research into topical microbicides is in progress. The National Institutes of Allergy and Infectious Diseases (NIAID) is funding topical microbicide research globally through its HIV/STD research program. Basic science investigation is underway to improve understanding of the vaginal and lower genital tract ecosystem in order to understand how sexual/mucosal infection occurs in women.
Clinical science must evaluate candidate microbicides and their delivery systems; establish safety and effectiveness profiles in both women and men; and develop successful behavioral interventions to ensure the acceptance and use of new products. Ideally, microbicides should be safe, effective, nonirritating to men or women, nonodorous, not too sticky, inexpensive, lethal to HIV and a broad range of STDs, have a long shelf life, and be safe for use at least twice daily. They should be able to be used without a partner's knowledge if necessary, and they should be formulated with and without contraceptive properties, so that women who wish to conceive can have anti-STD/HIV protection alone. Ethical issues in conducting microbicide trials include consideration of the potential toxicity of the products to the participants' partners and the difficulty of assessing independent efficacy without compromising current recommendations to include condoms in every trial.
The only product currently in use as a microbicide is the spermicide nonoxynol-9 (N-9). N-9 has been used since the mid-1980s as a spermicide alone and in combination with condoms, diaphragms and cervical caps. It comes in various delivery systems; foam, jelly, cream, film and gel. In the laboratory, N-9 has been shown to have microbicidal properties against HIV, gonorrhea and chlamydia. In clinical research, N-9 reduces transmission of gonorrhea and chlamydia by about 50%. Reducing these STDs may itself reduce risk for HIV transmission because infections in the vagina and cervix increase the number of circulating immune system cells, which are targets for HIV (for example, CD4 cells). A NIAID-sponsored phase III, randomized, placebo-controlled study of a film containing 75 mg of N-9, was recently conducted with women sex workers in Cameroon. Data from this study showed that using the film containing N-9 (vs. film placebo) had no independent effect on acquisition of HIV, gonorrhea or chlamydia when provided as part of an overall HIV/STD prevention campaign (which included providing condoms).
For nonapproved products, testing begins with in-vitro efficacy. Next is animal toxicity testing in which mucosal irritation and systemic absorption of the product is evaluated. Animal models have been developed at Pennsylvania State University in which human vaginal tissue has been grafted onto mice for toxicity testing. Formulation development of the product is also evaluated by animal efficacy and toxicity studies. Phase I clinical trials involve testing the product in small numbers of healthy women with "normal vaginas." These are women who are not having sexual contact and who will use the product in increasing doses and frequencies to observe for local and systemic responses.
New products are categorized as: (1) broad spectrum (i.e. detergents, antiseptics, spermicides, acid-buffers); (2) inhibitors of viral entry; (3) inhibitors of HIV replication (these are local formulations of anti-HIV drugs); and (4) combination products utilizing more than one mechanism of action. Except for the broad spectrum category (which includes N-9, octoxynol-9, benzalkonium chloride and chlorhexidine), none of the other products have yet been tested in phase II or phase III human studies. The following new products are under study at present:
Advantage-24 is currently the subject of NIAID-sponsored field testing in Kenya. The product is a new delivery system employing a gel that releases a low dose of N-9 over a 24-hour period, and is believed to "coat" the cervix. Advantage-24 is also in phase II rectal-use studies at the University of Washington, Seattle.
The Protectate sponge is a product containing both N-9 and benzalkonium chloride. It is undergoing testing in Canada.
Buffer gels are in NIAID-sponsored trials at Memorial Hospital in Providence, Rhode Island. These gels are microbicidal products designed to lower the vaginal pH, making the vagina more acidic. Since semen is quite alkaline, it raises the vaginal pH. The acid-buffer gel is being evaluated to see if it will keep the vagina acidic enough to kill pathogenic microbes, including HIV. Further testing is expected in sites in Asia and Africa.
Protegrin studies are being conducted at the University of California Los Angeles with NIAID funding. Protegrins are antibiotic protein fragments produced naturally by animals. Lab studies are ongoing to determine the activity of various formulations of protegrins against HIV and other pathogens.
Lactobacillus studies (again, NIAID-sponsored) are being conducted at the University of Pittsburgh under the direction of Sharon Hillier. Dr. Hillier and colleagues have determined that women who have naturally occurring lactobacillus bacteria in their vaginas have only half the risk of acquiring HIV as women without the protective bacteria. Lactobacilli produce hydrogen peroxide and other microbe-killing compounds. They also bring the pH of vaginal mucosa down to about 4.5. Phase I trials are testing whether use of a lactobacillus vaginal suppository can reduce transmission of gonorrhea and bacterial vaginosis. It is expected that phase II studies shortly will start enrolling female adolescents at high risk for HIV and STDs.
Pro-2000 is a product that blocks binding of HIV to cells' CD4 receptor, thus preventing the infection of new cells. Its corporate sponsor, Procept, is investigating its use as a topical microbicide in Belgium.
There is no simple path to achieving more effective methods for woman-initiated STD/HIV risk reduction. To make informed choices, women, educators and clinicians need to know what acceptable products are available at any given time, including the ones that are not 100% effective. Women who desire both pregnancy and protection from HIV/STDs may not have a safe and effective microbicide available in the foreseeable future.