Microbicide actions

Microbicides can act in various ways. Microbicides can be nonspecific, moderately specific or highly (exclusively) specific to HIV. The nonspecific and moderately specific agents are often active against a variety of sexually transmitted microorganisms (e.g., chlamydia and herpesvirus) and may have a contraceptive effect. The HIV-specific agents interact directly with one or several steps of the infection or replication cycle of HIV.

Nonspecific microbicides
The nonspecific microbicides consist of buffering agents and of detergents or surfactants that include nonionic, anionic or cationic compounds. The detergents destroy the viral envelope by solubilizing membrane proteins. However, this nonspecific mechanism of action may also disrupt the cell membranes of the vaginal and cervical epithelium and cause erosions and lesions, leading to an increased risk of HIV infection.

Moderately specific microbicides
Moderately specific microbicides mainly comprise  macromolecular linear anionic polymers. Linear polyanions are active against HIV, HSV and in some cases demonstrate inhibitory activity against human papillomavirus (HPV), Neisseria gonorrhoeae and Chlamydia trachomatis. They block viral entry into cells through electrostatic interactions with the viral envelope proteins and, in some cases, host cell receptors. The lack of potency of linear polyanions for HIV and the ability of semen to further abrogate anti-HIV activity, may in part explain the lack of in vivo efficacy of these microbicides. In addition, adherence to product use and transmission via anal receptive sex, which would not be prevented by a vaginally applied microbicide, are other considerations.

Highly specific anti-HIV agents
HIV-specific microbicides should preferentially block the viral infection cycle before the viral genome gets
incorporated in the target cells as proviral DNA.

Targeting viral entry seems the most promising method, preventing virus particles from entering its susceptible cells and, as shown or expected for most entry inhibitors, also preventing transmission of the virus from virus-infected cells to uninfected cells or transmission of dendritic cell-captured virus to lymphoid cells, or both.

The Future of Microbicide

Topical microbicides are a broad class of agents designed to block or kill infectious microorganisms directly at the site of transmission. With the AIDS pandemic continuing its unrelenting global march (40 million current infections, 14,000 new infections per day) driven largely by sexual transmission, microbicides have moved steadily toward the front line of preventative strategies.

Indeed, many candidate anti-HIV microbicides are currently under development, with several already in clinical trials. A battery of promising protein-based HIV inhibitors can potentially be developed, but they face serious challenges of high production costs and instability during transport and storage.

In a recent issue of PNAS, Rao et al. presented an intriguing version of a “live microbicide” approach whereby a commensal bacterium is engineered to secrete a potent anti-HIV peptide. When administered orally or as a rectal suppository, the bacteria would colonize the gut mucosa and secrete the peptide in situ, thereby providing protection in advance of exposure hopefully for days, weeks, or even months. This delivery mode would be highly advantageous over others requiring repeated topical application before each act of intercourse; also, the engineered bacteria would be relatively simple and inexpensive to manufacture, transport, and store.(An anti-HIV microbicide comes alive; Laurel A. Lagenaur and Edward A. Berger)

An antiretroviral microbicide gel can cut HIV infection in women by more than 50% if used consistently.
Most of the products tested previously as microbicides were either sulphated polysaccharides — which are intended to stop the virus from entering cells — or agents that prevent infection by killing either the virus or cells that carry it.

(Excerpt of) Potential Impact of Vaginal Microbicides on HIV Risk Among Women with Primary Heterosexual Partners

James M. McMahon, PhD, Associate Professor, Kathleen M. Morrow, PhD, Associate Professor, Margaret Weeks, PhD, Professor, Dianne Morrison-Beedy, PhD, RN, FNAP, WHAP, Professor and Dean, and Amanda Coyle, APRN, Senior Associate

Over the past 2 decades women have increasingly shouldered the burden of the global HIV pandemic (Joint United Nations Programme on HIV/AIDS [UNAIDS], 2004), with the majority of infected women acquiring HIV through sexual contact with a primary male partner (O’Leary, 2000). These trends are the result of multiple factors. Women may be biologically more susceptible to heterosexual transmission of HIV than men, especially via receptive anal intercourse (Boily et al., 2009; Mastro & Kitayaporn, 1998; Padian, Shiboski, & Jewell, 1991). 

In addition, gender-based social inequalities limit women’s options with regard to protective sexual behavior (Higgins, Hoffman, & Dworkin, 2010; Quinn & Overbaugh, 2005; Remien, Halkitis, O’Leary, Wolitski, & Gomez, 2005). Latex condoms, currently the only effective form of barrier protection against HIV, are under the control of men, who often are unwilling to use them, especially in the context of primary relationships (Conley & Collins, 2005).

Vaginal microbicides represent a female-initiated form of barrier and/or chemical protection that can potentially empower women with a means of self-protection. Vaginal microbicides are self-administered chemical compounds, most commonly in the form of a gel, that women can apply intravaginally prior to sexual intercourse to prevent or reduce HIV transmission. Modeling studies indicate that even a partially effective microbicide could have a major impact on the global HIV pandemic (Watts, 2002). 

About Personal Water Based Lubricant

Lubricant is a substance, typically fluid, that is used to reduce friction during sexual activity. Water-based lubricants are specifically those fluids or gels that are made from a base of water and typically a cellulose solution. A water-based lubricant is water soluble and can therefore be fairly easily washed off. The earliest and still most prevalent forms of personal lubricants are water-based, though newer forms of oil-based and natural lubricants have come onto the market.

Because they are water-based, such lubricants can have a tendency to dry out during use. This can be remedied to some extent by applying more of the lubricant or by applying a small amount of water to the area. A water-based lubricant will dry on its own and be absorbed into the skin or dissolve after use, leaving only the residue of the other ingredients. Because a water-based lubricant can dry out it is usually best to reapply during use to prevent a buildup of friction that can cause injury such as blistering or skin irritation.

Microbicides and women

Microbicides are substances capable of reducing the transmission of HIV and other sexually transmitted pathogens when applied vaginally.Evidence from many settings strongly suggests that many women will find microbicides easier to use than condoms and that they can be used when condom use is not possible. This has raised the concern that women might abandon condoms in favour of microbicides. Indeed, the fear of 'condom migration' has been a major barrier to the widespread endorsement of microbicides as a potential method of HIV prevention.

Despite such high HIV-efficacy, there is substantial evidence that in many settings levels of consistent condom use is low, especially within primary partnerships. Studies show that even after directed intervention, the percentage of couples that achieve consistent condom use seldom exceeds 20-30%, except where individuals know that one partner is HIV infected. Success in increasing the consistency of condom use has been greatest among sex workers and other vulnerable groups, but even here, many sex workers do not use condoms consistently with their non-commercial, primary partners.

Even when condoms are used consistently they may be used incorrectly. The immense gap between the numbers requiring protection and those using condoms consistently and correctly could potentially be filled by microbicides.

With AIDS vaccine efforts at an impasse, microbicides -- virus-blocking gels inserted into the vagina before sexual intercourse -- have risen from their own string of setbacks to once again offer hope of preventing HIV infections, at least in women.

Identifying a microbicide that works even partially could have a huge effect. Almost half of the more than 33 million people living with HIV worldwide are women; in sub-Saharan Africa, the figure is 60%.Abstinence and condoms have been the only proven ways to prevent or reduce the spread of HIV among adults. Circumcision lowers the risk for men, and already-existing AIDS drugs are used prophylactically to reduce mother-to-child transmission during birth or breast-feeding.

(The Excerpt of) Potential Impact of Vaginal Microbicides on HIV Risk Among Women with Primary Heterosexual Partners

James M. McMahon, PhD, Associate Professor, Kathleen M. Morrow, PhD, Associate Professor, Margaret Weeks, PhD, Professor, Dianne Morrison-Beedy, PhD, RN, FNAP, WHAP, Professor and Dean, and Amanda Coyle, APRN, Senior Associate

Over the past 2 decades women have increasingly shouldered the burden of the global HIV pandemic (Joint United Nations Programme on HIV/AIDS [UNAIDS], 2004), with the majority of infected women acquiring HIV through sexual contact with a primary male partner (O’Leary, 2000). These trends are the result of multiple factors. Women may be biologically more susceptible to heterosexual transmission of HIV than men, especially via receptive anal intercourse (Boily et al., 2009; Mastro & Kitayaporn, 1998; Padian, Shiboski, & Jewell, 1991). 

In addition, gender-based social inequalities limit women’s options with regard to protective sexual behavior (Higgins, Hoffman, & Dworkin, 2010; Quinn & Overbaugh, 2005; Remien, Halkitis, O’Leary, Wolitski, & Gomez, 2005). Latex condoms, currently the only effective form of barrier protection against HIV, are under the control of men, who often are unwilling to use them, especially in the context of primary relationships (Conley & Collins, 2005).

Vaginal microbicides represent a female-initiated form of barrier and/or chemical protection that can potentially empower women with a means of self-protection. Vaginal microbicides are self-administered chemical compounds, most commonly in the form of a gel, that women can apply intravaginally prior to sexual intercourse to prevent or reduce HIV transmission. Modeling studies indicate that even a partially effective microbicide could have a major impact on the global HIV pandemic (Watts, 2002). 

While it is anticipated that the first generation of vaginalmicrobicides will be less effective at preventing HIV than latex condoms, the enormous potential of this new technology lies in its enhanced acceptability and usability by women. As our experience with the female condom has demonstrated, the importance of the acceptability of any new HIV prevention technology cannot be overstated (Kaler, 2004). It is therefore critically important that the public health sector in the United States prepare for the introduction of commercially available vaginal microbicides (Van de Wijgert & Coggins, 2002). While many American women have expressed a keen interest in vaginal microbicides (Darroch & Frost, 1999), the issues surrounding their acceptability and preference in relation to condom use are complex and have not received adequate attention. One complexity involves the potential reduction of condom use that might result from the introduction and adoption of microbicides.

Things to Consider Before You Buy Vaginal Lubricants

Vaginal lubricants are available in a variety of products containing various ingredients.
It's important for women to read the label of a vaginal lubricant and buy only water-based vaginal lubricants.
Petroleum-based lubricants can harbor bacteria in the vagina and lead to infection, as well as cause damage to latex condoms rendering them ineffective against unplanned pregnancy and STDs.

Many times women believe that vaginal lubricants or moisturizers are only for women going through menopause and experiencing vaginal dryness; however, normal estrogen fluctuations often cause vaginal dryness creating the need for extra vaginal lubrication.

Vaginal dryness often occurs during:
• the menstrual cycle,
• pregnancy,
• childbirth,
• nursing,
• times of emotional stress,
• and when using a condom.

The Best Type of Vaginal Lubricant
There are several different types of vaginal lubricants available over-the-counter, as well as estrogen-based creams available by prescription.
Vaginal lubricants come in tubes, bottles, and as vaginal suppositories.
Which product works best for your situation is mostly a matter of personal preference.

Gardnerella & Candidiasis (3)

CAUSES OF CANDIDA PROLIFERATION 

- A diet rich in sugar, white flour, and acidic foods.
These are candida's favourite nutrition.

- Pregnancy.
The high levels of progesterone for nine months may cause current colonies of candida to grow in size. Specifically if the mother has lived with a diet rich in sugar and white flour before and during her pregnancy. (Please note. Candida can be passed from the mother to the baby during birth. And candida can cause much discomfort in a baby. Furthermore, baby formulas could be high in sugar and feed the baby's candida.)

- Contraceptive pills.
These pills are very high in progesterone, and because a woman typically takes pills longer periods, this provides a happy environment for the candida to thrive.

- Antibiotics (including antibiotics in commercially-raised beef, chicken and fish).
Antibiotics kills off both bad and good bacteria. The good bacteria it kills off in our intestines is the lactobacillus acidophilus. It lives side by side with the candida albicans, and contributes to the health of our digestive system. However, when a round of antibiotics kills the lactobacilli, that leaves our intestines in an acidic environment (candida loves acidic), which then allows the spread of the candida colony into the space left empty by the dead lactobacilli.

Gardnerella & Candidiasis (2)

What You Should Know About Candidiasis

Candidiasis, (commonly known by other names thrush, yeast infection, fungal infection) like diabetes, has been dubbed a 20th-century disease, proclaimed widespread and charged with causing complaints such as allergies, migraines, mental disorientation, bloating, skin complaints, and at their worse, organ failure and cancer.

Candidiasis, or yeast infection, is a stealthy attacker, in that it mimics symptoms of other illnesses and thus go unidentified as candida. That is the reason candida population can bloom in our bodies unchecked until it has proliferated well into every part of our system (systemic candida).

The problem with mainstream medical professionals is that a large number of them do not believe in the dangers posed by candida. Instead they treat the symptoms that manifest clearly – allergies, coughs, chronic bronchitis, and such, without knowing that the medications prescribed may actually make the yeast infection worse.

Take allergies for example. Allergies have mystified health practitioners for decades. And yet, although the candida-allergy connection had been discovered and confirmed by biological technologists and natural health therapists since the 1970s, it is yet to be a recognised branch in the study of conventional medicine. Research studies show that to control yeast infections would ultimately cure most allergies, because an uncontrolled growth of candida in our blood system is a major cause of allergic reactions to chemicals in our food, air and water.

Candida yeast are a normal component of healthy flora existing in our bodies. They are tiny, microscopic plants that love warm, dark and moist environment, and so seek places like the intestines, the walls of the vagina, and when systemic (all over our body) the blood vessel linings and mucous membranes of our organs. Because they are plants, candida yeast have roots, stem and foliage. They sink their roots into the mucous membranes of the body, which, to candida, are fertile soil.

Gardnerella & Candidiasis (1)

When women are experiencing issues with their reproductive tract it's important to determine what the problem is and the way to treat it best.
In the case of Gardneralla and vaginal Candidiasis it can be confusing for women to know which one of these infections they might have.

This is a problem since Gardnerella and Candidiasis are treated in entirely different ways.

If a woman thinks she has Candidiasis and then goes and gets an over the counter treatment for yeast infections, but at the same time has Gardnerella, then she is not only wasting her money, but also not treating the infection.
Infections left untreated only get worse.

Gardnerella is caused by bacteria infecting the female reproductive tract and it is referred to as bacterial vaginosis.

This overgrowth of bacteria can be brought on by having unprotected sexual intercourse with a partner who is infected with the Gardnerella vaginalis bacteria, however, it has been contracted in some cases non-sexually too.

Women with Gardnerella will have a grey or yellowish discharge when infected and it will produce a strong fishy odor especially when washed with alkaline based soaps.

Women will experience little to no irritation when infected with Gardnerella and the noticably symptom is the odor.

A doctor will prescribe an antibiotic to treat the infection and sexual partners should also be treated.

Douching can help with the odor, but will not treat the infection.


Vaginal Candidiasis

Candidiasis, on the other hand is caused by the fungus Candida albicans and occurs when there is an overgrowth of the yeast cells in the vagina as a result of antibiotics, weakened immune systems, poor diet, or sexual transmission.

Qualities a Microbicide Should Have

A Microbicide should:

-applicable several hours prior to intercourse
-not messy or "leaky"
-able to be applied easily and evenly around the vagina as well as cervix
-long-acting
-look, smell and taste fine
-able to avoid infection with no disrupting or irritating the delicate tissues
-bioadhesive (able to develop protective barrier against STD pathogens)
-protective against a variety of STDs
-acid-buffering (maintains regular acidity [pH] of vagina in presence of sperm)
-protective of natural vaginal environment ("friendly flora"), possibly even improving natural vaginal defense mechanisms

Some of the Microbicide's ingredients

These are some of the microbicide's ingredients:

Benzalkonium Chloride (Bzk)
Benzalkonium chloride, also known as alkyldimethylbenzylammonium chloride and ADBAC, is a mixture of alkylbenzyldimethylammonium chlorides of various even-numbered alkyl chain lengths. This product is a nitrogenous cationic surface-acting agent belonging to the quaternary ammonium group. It has three main categories of use; as a biocide, a cationic surfactant and phase transfer agent in the chemical industry.

BZK demonstrates potent in vitro activity against the majority of microorganisms causing sexually transmitted infectious diseases, including those acting as major genital cofactors of HIV transmission and associated with high morbidity or mortality. (In vitro inactivation of Chlamydia trachomatis and of a panel of DNA (HSV-2, CMV, adenovirus, BK virus) and RNA (RSV, enterovirus) viruses by the spermicide benzalkonium chloride
Laurent B-leca,b,*,  Carol Tevi-Benissana,  Anne Bianchic,  Sylvie Cotignya, Maria Beumont-Mauvielc,  Ali Si-Mohameda and  Jean-Elie Malkinc)

Xylitol
Xylitol is an organic compound with the formula (CHOH)3(CH2OH)2.Xylitol has no known toxicity in humans.

Xylitol is a sugar alcohol sweetener used as a naturally occurring sugar substitute. It is found in the fibers of many fruits and vegetables, and can be extracted from various berries, oats, and mushrooms, as well as fibrous material such as corn husks and sugar cane bagasse. Xylitol is roughly as sweet as sucrose with only two-thirds the food energy.

Microbicide Q & A (3)

How would an HIV microbicide function?
An HIV microbicide could work in 5 different ways:
- Eliminating or inactivating pathogens.
A microbicide could inhibit HIV infection by breaking down the surface of the virus or pathogen.
- Create physical barriers. Gels or creams could offer a physical barrier between pathogens or viruses, and susceptible cells in the epithelium (cell wall) of the vagina or rectum.
- Strengthening the body's natural protection.
The body has numerous naturally sourced defense system that a microbicide might be able to supplement or enhance. For example, lactobacillus is a naturally occurring, "good" bacteria that helps protect the vagina by keeping its acidic environment. This natural acidity helps foster an inhospitable environment for a lot of pathogens, including HIV. A microbicide that supports the lactobacilli in carrying out this function might inhibit infection by HIV or STDs.
- Inhibiting viral entry.
A microbicide could inhibit viral or bacterial infection by interfering with the binding of viral proteins to cellular receptors. For example, infection with the HIV virus happens through binding of gp120 (on the outside of the virus) to receptors on a cell's membrane. A potential microbicide might interrupt this process by binding to receptors ahead of time, thus blocking the sites and preventing HIV attachment to the cell.
- Suppressing viral replication. Designed as gels or creams, anti-HIV medications that are already FDA-approved and available might be able to reduce replication of HIV in the vagina or rectum during sexual intercourse.

Microbicide Q & A (2)

Who is working on microbicide research and development?
Virtually all microbicides research to date has been conducted by non-profit and academic institutions or small biotech companies. Research is financed by charitable foundations along with government grants. These public funds also support basic science, social and behavioural research, and clinical study infrastructure that contribute to microbicides research and development. Large pharmaceutical companies have not invested significantly in this area, this is mostly because their income would be minimal.

Why do we need microbicides if we will finally have an HIV-vaccine?
No method or technology will "solve" the AIDS pandemic. We must implement all existing prevention methods --such as behavior change, voluntary counselling and testing, STI diagnosis and treatment, extensive access to male and female condoms, and anti-retroviral interventions-- as well as extend our collection of resources and technologies. Microbicides will probably be accessible and available sooner than an HIV-vaccine. Even after a safe and effective vaccine is discovered, vaccines and microbicides will have different, complementary roles to play in an integrated, multi-faceted global HIV prevention strategy.

Would a microbicide also protect the male partners of HIV positive women?
Lots of candidate microbicides currently being examined are widely anti-microbial and may provide protection against a variety of sexually transmitted infections, including HIV.  By neutralising pathogens in both semen and vaginal secretions, these products will give bi-directional protection; that is, will help protect men and partners. This will give HIV positive people a way of minimizing their partner's risk of HIV exposure during intercourse --as well a way of reducing their own risk of re-infection.
Microbicides will also provide valuable back-up protection to couples who use them with condoms. If the condom slips or breaks, the microbicides can provide both partners added protection from possible infection.

Why would a man want to use a microbicide instead of a condom?
Lots of men dislike using male condoms, regardless that they are excellent barriers against infection and unintended pregnancy. Objections include perceived decrease in pleasure, difficult maintaining an erection, interruption of spontaneity and decrease of the intimacy associated with skin to skin contact. Even before the spread of HIV/AIDS resulted in higher concern about STIs, these factors influenced men's attitude towards condoms. Largely, they account for the popularity of non-condom methods of contraception.
However, non-condom methods of STIs prevention do not yet {exist|be found}. Even when microbicides reach the market, it is unlikely that they will meet the efficacy of male and female condoms for HIV prevention. Logically, it is advisable to keep a virus from coming into contact with one's body than it is to try to eliminate it once it is there.
But, for men and women who don't use condoms regularly, microbicides will offer an essential risk reduction option. Using even a partially effective microbicide will provide significantly more protection than using nothing at all.

Microbicide Q & A (1)

What is a microbicide?
A microbicide is a compound that eliminates micro-organisms.

What does a microbicide do?
Topical microbicides, applied to lining of body cavities, work as chemical barriers to avoid the spread of Sexually Transmitted Diseases (STDs).
An HIV microbicide provides the potential for a protection choice that both women and men could effortlessly control, with or without the consent or knowledge of their sexual partner.

What forms can a microbicide come in?
A microbicide could be produced in various forms including gels, creams, suppositories, films, or in combination with a sexual lubricant.

Will different HIV microbicides be necessary for vaginal and rectal use?
Probably.
Different microbicides will be necessary for the vagina and for the rectum because of differences in their physical structure and properties.
An effective rectal microbicide must take into consideration that HIV is more easily transmitted during anal rather than vaginal intercourse.

Will a microbicide cure AIDS?
No, a microbicide is not a remedy for those already infected with HIV.
Instead, it would be an HIV prevention option, impeding (or halting) the transmission of HIV.

Microbicides benefits

- Will provide women an easy way to minimize their personal risk of infection when they cannot insist on   condom use.
- May provide bi-directional protection for men sex with partners who are HIV positive or have STIs.
- Helps protect the wellness of children by helping to lower their parents' risk of infection.Prevent from HIV and STIs while still allowing you to conceive a child.
- Help protect your future children from being born with HIV and/or other STIs.
- Provide you with extra resources for making safe, informed reproductive choices.
- Offer protection against both unwanted pregnancy and diseases.
- Offer a contraceptive alternative that is non-hormonal, non-irritating, and will not interfere with intimate contact.
- Be usable with condoms or hormonal contraceptives for back-up protection.
- Provide contraceptive safety and minimize risk of infection when condoms are not being used.
- Enable you to enjoy sex with less fear of becoming infected.
- Provide lubrication thereby enhancing sexual pleasure and enjoyment.
- Be applied before sex to avoid interruption

How microbicide works & its efficacy

How Will They Work?

"Microbicide" is simply a common term put on anything created to prevent contamination by HIV and other sexually transmitted pathogens when applied in the vagina or rectum. Since HIV and STI (sexually transmitted infection) pathogens can attack your body in various ways, an effective microbicide should stop this attack at several stages in the infection process.

Each uses at least one of these five basic mechanisms of steps:
# Eliminating or inactivating pathogens.
Some microbicides work by breaking down the top or envelope of the virus or pathogen.

# Developing physical barriers.
Microbicides could give you a physical barrier between pathogens and vulnerable cells in the epithelium (cell wall) of the vagina or rectum.

# Building up your body's normal defenses.
The body has many naturally sourced immunity process that a microbicide may be able to supplement or boost.
Lactobacillus, for example, is a naturally occurring, "good" bacteria that can help protect the vagina by keeping its acidic environment.
This natural level of acidity allows an inhospitable environment for most pathogens, including HIV.
Therefore, a microbicide that supports the lactobacilli in performing this purpose is one potential procedure of action being explored.

# Inhibiting viral entry.
Some microbicides bind to viruses and bacteria in order to prevent them from binding to and infecting healthy cells.

# Suppressing viral replication.
Some microbicides are being developed from the antiretroviral medicines that HIV-positive people use to reduce the quantity of virus in their bodies.
Designed as gels or creams, these medicines may be able to restrain replication of HIV that enters the vagina or rectum during intercourse.
In that case, they could significantly lower the chances that the microbicide user will become infected or re-infected (if already HIV-positive).
Microbicides may also be combined with physical barriers for higher performance.

About Microbicide

Every day, approximately 14,000 people around the world are newly infected with HIV; of these, almost half are women. Even as they encounter increased risk, many women have minimal control over HIV/STD prevention decisions. Microbicides could change this reality. Microbicides are products applied directly to the vagina or rectum that minimize the risk of transmitting STDs. Microbicides containing contraceptive agents may also facilitate fertility regulation.

Microbicides, the compounds and formulations that can prevent transmission of sexually transmitted diseases (STDs)/HIV are being pursued actively as a promising AIDS intervention. Microbicides for sexually transmitted diseases, are pharmacologic agents and chemical substances that are capable of killing or destroying certain microorganisms that commonly cause human infection, for example the human immunodeficiency virus. Microbicides are a diverse group of chemical compounds that exert their activity by a variety of different mechanisms of action.