header_n.gif (7845 bytes)

Briefing Document 32

HIV and Microbicides

This Briefing Document explores issues surrounding HIV/AIDS and Microbicides, including definitions of microbicides, and why microbicides are important. Also examined are products under developement, ethical considerations of testing microbicides and questions to be considered.

Briefing Document #32 is one of an on-going series. Visit the catalogue of Briefing Documents.

The Briefing Documents are created by
AIDS Calgary Awareness Association

 aclogosm.gif (2652 bytes)

 

 

What is a microbicide?

Microbicides are substances that can be used to combat infection1. A microbicide can substantially reduce the transmission of sexually transmitted infections (STIs) when applied in either the vagina or rectum1.

 

Why are microbicides important?

Globally, the spread of HIV and other STI’s have important impacts on the health of individuals and nations. Worldwide, prevention activities have focussed mainly on efforts to reduce risky sexual behaviour1. The efforts involve encouraging individuals to abstain from sexual intercourse, or use condoms every time they have sex. In addition, harm prevention programs such as needle exchange, screening of donor blood supplies and c-sections to limit vertical transmission have been implemented. Efforts to prevent STIs based on safer sexual behaviour have been hampered by several factors, which impact women especially.

  • Many women are unable or unwilling to insist that their partner use a condom every time they have sex. Many women lack the authority in a sexual relationship to insist on consistent condom use or mutual fidelity1.
  • Some women do not have sufficient self-confidence or financial independence to walk away from a relationship in which their partner’s refusal to use a condom places them at risk2
  • Women are fearful that a request for condom use may be interpreted as suspicion of their partner’s infidelity or acknowledgement of their own1.
  • Women do not want their partner to use a condom because they wish to become pregnant1.
  • Some women who believe they are in a mutually monogamous relationship with an uninfected partner do not know that their partner has other partners2.

94% of women indicated that they would be at least"somewhat" interested in using a vaginal microbicide if it was available2

In reality, the decision to use a condom - either male or female - rests with the male partner. Based on the barriers which women face, there is increased interest in a female- controlled method of HIV prevention. Microbicides offer an important new prevention alternative for individuals and couples who are unable or unwilling to use condoms.

 

Microbicidal Products

Over fifty new products are currently being investigated for use as microbicides3. Some are completely new compounds while others are based on existing products but used in new ways or combinations.

Antibodies - Antibodies are part of the body’s natural defence system and have been the basis of vaccine technology. Researchers have identified and isolated the antibodies which counteract HIV and have managed to reproduce them3. These technologies would be based on the idea that the antibodies could be delivered directly to the vagina , where they could combat the pathogen before infection has occurred4.

A major hurdle is that antibodies are incredibly expensive to produce. A drug company in San Diego has recently suggested producing them cheaply in transgenic rice plants. The company has already created such plants to produce antibodies to herpes simplex3.

Detergents and surfactants - Surfactants are detergents that disrupt microbial and sperm membranes by emulsification. These products disrupt the outer membrane of cells and the outer shell of viruses4. The best-known such product is the over-the-counter spermicide Nonoxynol-9 (N-9)4 .

Surfactant containing creams and gels have the advantage of being very broad in their killing ability, but they can damage cell membranes as well as those of the unwanted pathogens. A common observation has been that N-9 causes thinning and irritation of vaginal walls3. At the Microbicides 2000 conference, researchers showed that when used anally, N-9 leads to cell shedding and irritation of the rectum, leaving a large area especially susceptible to viral infection3.

Another detergent that is used as a spermicide (octoxynol-9) is being explored as a potential microbicide, as are products which are used in shampoo, toothpaste and contact lense solution1.

pH Regulators - pH regulators maintain the natural acidity ( pH) level of the vagina, making it inhospitable to HIV. The virus cannot live in the normal acidity of the healthy vagina; however, semen is alkaline and the vagina becomes more alkaline during intercourse, allowing HIV to survive1.

One type of bacteria - Lactobacillus Crispatus (LB) helps keep the vagina free from infection by producing hydrogen-peroxide , a substance that is highly acidic3. LB is one of many bacteria that live normally in the healthy vagina. When the ecology of the vagina is somehow disrupted due to infection, douching or poor hygiene, the LB bacteria can die off, leading to a condition known as Bacterial Vaginosis (BV). BV has been linked to an increased risk of HIV infection. Studies are under way in the US to test the human safety of LB suppositories3.

 

Antibiotic Peptides - Antibiotic peptides are small protein molecules that line every surface of the body - eyes, skin, lung, intestinal tract - and kill bacteria within minutes of contact. If applied in concentrated quantities at the site of potential infection, peptides

may kill off pathogens before they cause infection1.

 

 

Anti-retrovirals -Anti-retroviral products interrupt the replication of the virus once it enters a cell1. Many retroviral drugs initially explored as potential AIDS therapies were abandoned because they were not easily absorbed into the bloodstream. Although these compounds may not work as therapies, they might work as vaginal microbicides, because they could be applied to the skin and would not need to be absorbed systemically1.

Carrageenan -The Population Council is developing a family of microbicides based on the food thickener Carrageenan4. Carrageenan is a seaweed ( red algae) derivative that turns into a gel when mixed with water. It is a very large starch molecule which contains negatively charged sulfate groups.

The negative charge causes Carrageenan to stick to viral envelops and possibly target cell membranes. Carrageenan disrupts the process by which viruses stick to and invade cells. Carrageenan may also impair some bacteria but appears to have no effect on sperm4.

Currently, the carrageenan compound PC-515 is categorized as GRAS (‘generally recognized as safe") by the FDA and is very cheap to make3. It remains in place for up to 18 hours but cannot pass into the body because of it’s size. PC-515 is currently undergoing phase 2 studies in Thailand and South Africa. It is estimated that final testing of this product will take at least five years3.

 

Practical and Ethical Dilemmas in the Clinical Testing of Microbicides

To test the efficacy of microbicides, highly complex trials involving thousands of individuals who are at substantial risk of HIV and other sexually transmitted infections. The emerging problem is how to achieve scientifically rigorous results in an ethically sound manner5. These issues don’t just apply to the testing of microbicides but are also applicable to the testing of HIV vaccines and shortened AZT regimes to prevent vertical transmission5.

  • Pharmaceutical companies have been reluctant to invest in microbicide development because of questions regarding the profitability of such products. The money required to bring a product through clinical testing and to market is in the neighbourhood of $200 million dollars5.
  • As a result, the public sector must take a lead in this area by making research grants available for specific development of these products and by partnering with small companies to help evaluate their products5.
  • Microbicide research should be embedded within a larger commitment to address the full range of factors that place women at risk of sexually transmitted infection5.
  • Although women need and deserve a technology that they can control, microbicide research should not be allowed to distract attention from the underlying power inequities that put women at risk5.
  • Several products should be moving through testing and development at the same time. Only a very small percentage of products ever make it to market. Products are eliminated at several points along the process. Unless the numbers of products being investigated is increased, the probability of finding a viable product in a reasonable period of time is poor5.
  • Randomized controlled trials are the most appropriate way to establish whether a microbicide reduces STI/HIV transmission. Individuals would be randomized into one of two arms, with those in the first arm receiving condoms and a candidate product. The other arm of the trial would receive condoms and a placebo product fashioned to resemble the candidate microbicide. All individuals would be counselled to use both a condom and the vaginal product at each act of intercourse5.
  • Trials should be multi-site in both industrialized and developing countries, in order to share the burdens and benefits of research and to increase the generalizability of results5.
  • Because a large number of study participants would be needed, any efficacy trail of a candidate microbicide would likely require a collaboration between several sites in order to enroll sufficient numbers of people. To date, researchers have focussed on sex trade workers in order to test products, but trials should include women from all walks of life5.
  • From an ethical standpoint, it is highly desirable that women in all countries that are likely to benefit from a microbicide also share the burden of research. By testing in several locations, the efficacy of a microbicide can be established in a number of conditions and social situations5.
  • All trials should include active, appropriate efforts to promote consistent condom use by all trial participants. These efforts may require partnering with NGO’s to ensure that counselling is provides in the most effective, appropriate manner for the context of the community. There is also a need to ensure that procedures to obtain informed consent and convey product information are tailored to the needs of the community5.
  • Women are likely to prefer a variety of product characteristics and formulations, so multiple formulations should be pursued. These products can be in the form of gels, foams, suppositories, as well as formulations with and without contraceptive properties5.
  • Investigators should be aiming for an over-the-counter product that can be widely available through multiple channels without a prescription5.
  • Drug resistance on the part of the microbicides would remain an issue. This is the case with any medication or intervention with a microbe-specific target of action rather than general activity , such as pH modification5.

 

Questions to Consider

Many questions about potential microbicides still need to be resolved. These include the potential of a microbicide developed for vaginal use to be adapted for rectal use, how long particular products will be effective once applied, their safety over long periods of repeated use, formulation and whether it would be prescription or available over the counter3. There is a demand for non- contraceptive forms of microbicides for women wishing to become pregnant as well as to improve their acceptability and use in countries where contraception is frowned on by the Catholic Church2.

 

Next Steps

In Canada, the first trials of a microbicide have begun at Laval University in Quebec. The product is described as an" invisible condom" which is applied as a liquid but turns to gel at body temperature6.

Although this is a promising step, it is likely to be years before this product reaches women, assuming that all trials go smoothly. In the mean time, there is interest in advocating for increased funding and support for microbicide research in Canada. The Canadian Aids Society (CAS) has developed a community mobilization kit which includes sample letters to government ministers and sample op/ed letters which can be used to raise awareness of the need to focus energy and money on microbicide research4.

References

  1. The Terrence Higgins Trust. Briefing on Microbicides: Prevention for Women. http://www.iapac.org/clinmgt/women/microb.html
  2. The Allan Guttmacher Institute. Microbicides:A New Defense against Sexually Transmitted Diseases.
    http://www.agi-usa.org/pubs/microbicides.html
  3. Gilden, Dave. Feasible Microbicides Remain an Elusive Goal - Conference Proceedings - Microbicides 2000.
    http://199.105.91.6/treatment/insider/mic.asp
  4. Canadian Aids Society. Community Mobilization Kit - Microbicides: A Female-Controlled Method of Preventing HIV and other Sexually Transmitted Diseases. 2000.
  5. The Population Council and Women’s Health Advocates on Microbicides (WHAM). Practical and Ethical Dilemmas in the Clinical Testing of Microbicdes: A report on a symposium.
    http://www.iwhc.org/micropub.html
  6. Canada funds trial of "invisible condom"
    http://dailynews.yahoo.com/h/nm/20000602/hl/canada_condoms_1.html

 

News, Features & FAQ's | Events & Fund Development | Services, Programs & Stuff | Web Links & Articles | Home

aclogosm.gif (2652 bytes)

Copyright � 1998-2002
AIDS Calgary Awareness Association
Suite 200, 1509 Centre St South
Calgary, AB T2G 2E6
Tel: (403) 508-2500, Fax: (403) 263-7358
Web: www.aidscalgary.org
Questions? Send email to [email protected]

Read about this web site. Created & maintained by Humantec Consulting. Comments about the site can be sent to Humantec Consulting.

Thanks to Shane H, our first Web volunteer, for getting us started.