Microbicide: Prevention from HIV and Other STDs

The danger of the HIV and STDs to people’s health and life has led scientists do research more about the prevention that can protect them from the infections. Tendency to do research for the prevention than the treatment happens because the infections are able to kill people. Logically, it will be easier and better to prevent than cure. The prevention will help more than treatment.

Microbicide is one of the inventions for the prevention of HIV and other kinds of STD. The compounds or the substances of the microbicide will help to reduce the infection possibility from virus, bacterium, fungus, and any kind of microorganism. Topical microbicide can be used in the condom or in the genital organs directly. It is applied to prevent the infection to transmit.

The method of the prevention is getting easier to be done. The microbicide helps people to protect themselves from HIV and STD simpler. However, the method which is published is quite political. Then, microbicide can be the break of the political prevention of HIV and STDs. This can be controversial, but, it can be suitable or even better in certain kind of situation.

Microbicide for women will very useful. The chance of the infection of HIV and STD for women is quite high through sexual contact. Women sometimes do not have control to make the men use condom for the safe sex. Then, it will be better for women to use microbicide which can prevention infection of HIV and other STDs. From all the explanations of the use of microbicide, that the microbicide will decrease the number of the infected people.

Microbicide &Safe Sex (10)

PID

Pelvic inflammatory disease (PID) is an infection of the female reproductive organs. It usually occurs when sexually transmitted bacteria spread from your vagina to your uterus and upper genital tract. Many women who develop pelvic inflammatory disease either experience no signs or symptoms or don't seek treatment. Pelvic inflammatory disease may be detected only later when you have trouble getting pregnant or if you develop chronic pelvic pain.

Symptoms in PID range from subclinical (asymptomatic) to severe. If there are symptoms, then fever, cervical motion tenderness, lower abdominal pain, new or different discharge, painful intercourse, or irregular menstrual bleeding may be noted. It is important to note that even asymptomatic PID can and does cause serious harm. Laparoscopic identification is helpful in diagnosing tubal disease, 65–90% positive predictive value in patients with presumed PID. Regular Sexually Transmitted Infection (STI) testing is important for prevention. Treatment is usually started empirically because of the serious complications that may result from delayed treatment. Definitive criteria include: histopathologic evidence of endometritis, thickened filled fallopian tubes, or laparoscopic findings. Gram-stain/smear becomes important in identification of rare and possibly more serious organisms.

A woman can get PID if bacteria (germs) move up from her vagina and infect her pelvic organs. Many different types of bacteria can cause PID. But, most cases of PID are caused by bacteria that cause 2 common sexually transmitted infections (STIs) — gonorrhea and chlamydia. It can take from a few days to a few months for an infection to travel up from the vagina to the pelvic organs.

You can get PID without having an STI. Normal bacteria found in the vagina and on the cervix can sometimes cause PID. No one is sure why this happens. You can get pelvic inflammatory disease without having an STI. Normal bacteria found in the vagina and on the cervix can sometimes cause pelvic inflammatory disease. No one is sure why this happens.

Microbicide & Safe Sex (9)

HPV

Human papillomavirus or HPV, is the name for a group of viruses that includes more than 100 types. More than 40 types of HPV can be passed through sexual contact.

The types of HPV that infect the genital area are called genital HPV. Over half of sexually active people will have HPV at some point in their lives. But most people never know it. This is because HPV most often has no symptoms and goes away on its own.

HPV is passed on through genital contact, most often during vaginal and anal sex. HPV may also be passed on during oral sex and genital-to-genital contact. HPV can be passed on between straight and same-sex partners—even when the infected partner has no signs or symptoms.

A person can have HPV even if years have passed since he or she had sexual contact with an infected person. Most infected persons do not realize they are infected or that they are passing the virus on to a sex partner. It is also possible to get more than one type of HPV. Very rarely, a pregnant woman with genital HPV can pass HPV to her baby during delivery. In these cases, the child can develop Recurrent Respiratory Papillomatosis (RRP), a rare condition in which warts grow in the throat. In children, this is also referred to as juvenile-onset Recurrent Respiratory Papillomatosis (JORRP).

Microbicide & Safe Sex (8)

HIV/Aids
Persons initially infected with HIV may develop an "acute retroviral syndrome" characterized by fever, lymph node enlargement, and flu-like symptoms. If symptoms are present, they clear spontaneously, but all infected persons, both with and without symptoms, remain infected and infectious to others indefinitely. The incubation period is highly variable, averaging about a decade, but ranging from a few months or years to possibly longer than two decades. When sufficient damage to the immune system has been sustained, measured either by laboratory cell counts of the Thelper cells or by onset of opportunistic infections, the patient is said to have AIDS. Common manifestations of HIV infection include tiredness, lymph node enlargement, fever, weight loss, and yeast infections of the mouth and vagina.

HIV infection is diagnosed by laboratory detection of evidence of infection, usually identification of HIV-specific antibodies in a blood, oral fluid, or urine specimen. AIDS can be diagnosed in HIV-infected persons in several ways, based on either laboratory evidence of immunodeficiency (lowered levels of CD4+ cells), or clinically by onset of any one or more of a specific list of opportunistic diseases. Opportunistic diseases are those that occur only, or most severely, in patients whose immune systems are impaired. The most common opportunistic diseases in AIDS patients are Pneumocystis carinii pneumonia, Kaposi's sarcoma, toxoplasmosis of the brain, tuberculosis and other mycobacterial infections, and severe herpes, cytomegalo virus, and yeast infections.

How the AIDS Virus Works?
The AIDS virus weakens the immune system (“immune deficiency”), allowing other infections to ravage the body. These infections are called “opportunistic” because they take advantage of the opportunity to live where the body’s immune system would normally destroy them. It’s when these opportunistic infections strike that the person is said to have AIDS.

Microbicide & Safe Sex (5)

STD Gonorrhea Information
Gonorrhea sometimes mistaken for the clap (Chlamydia) isn't really an STD (Sexually Transmitted Disease) but actually an STI (Sexually Transmitted Infection). It's caused by bacteria called Neisseria gonorrhoeae which lives in the sexual organs including the urethra and reproductive tracks of both men and women.
Gonorrhea has one of the highest infection rates. In the USA It's estimated that almost one million people a year are infected with this STD. The most effected are young adults and teens mostly because of there high promiscuity rate between them.
Like most STDs and STDs it is contracted through sexual contact. Including coming in contact with the penis, vagina, anus, and even the mouth and throat. It is very easily transmitted from one person to another, which is why Gonorrhea has such a high rate of infection. On top of that the new strains of Gonorrhea are becoming increasingly harder to treat as they are adapting to the antibiotics used to treat them.

Gonorrhea Symptoms Do I Have Gonorrhea?
Gonorrhea symptoms are generally mild to non existent. When there are symptoms of Gonorrhea they will usually become noticeable between 5 and 30 days and differ slightly between men and women. Since gonorrhea lives in the sexual organs and in the throat these are the primary places to be aware of when wondering if you have gonorrhea symptoms.

Microbicide & Safe Sex (4)

Genital Warts

Genital warts (or Condylomata acuminata, venereal warts, anal warts and anogenital warts) is a highly contagious sexually transmitted disease caused by some sub-types of human papillomavirus (HPV).
Genital warts are flesh-colored or gray growths found in the genital area and anal region in both men and women.

It is spread through direct skin-to-skin contact during oral, genital, or anal sex with an infected partner.
Genital warts affect both men and women and can occur at any age.
Most patients with genital warts are between the ages of 17-33 years. Genital warts are highly contagious. There is around a 60% risk of getting the infection from a single sexual contact with someone who has genital warts.

Whilst of those infected with genital HPV it is estimated that only a "small percentage" (between 1% and 5%) develop genital warts, those infected can still transmit the virus. Other types of HPV also cause cervical cancer and probably most anal cancers, however it is important to underline that the types of HPV that cause the overwhelming majority of genital warts are not the same as those that can potentially increase the risk of genital or anal cancer.

Although genital warts are painless, they may be bothersome because of their location, size, or due to itching.

You can’t get genital warts from hugging, sharing baths or towels, from swimming pools, toilet seats, cups or cutlery.

Symptoms
Genital warts are usually painless and do not pose a serious threat to a person’s health. However, they can appear unsightly and cause psychological distress.

Microbicide & Safe Sex (3)

Chlamydia
Click here to learn about Chlamydia and click here to learn about Chlamydia Home Test.

Cytomegalovirus (CMV)

Cytomegalovirus (CMV) is a common virus.
CMV is part of the herpes family of viruses. As with most other herpes-type viruses, once you are infected with CMV, it will remain inactive in your body for the rest of your life. CMV causes few symptoms in most people.

CMV is spread through bodily fluids, such as saliva and urine. It can be passed on through close bodily contact. For example, the infection can be found in small droplets of saliva which are spread from one person to another when an infected person coughs or sneezes.

Unlike many viral infections, CMV usually causes few if any symptoms. Most people do not know they have (acquired) an infection.

The symptoms of cytomegalovirus (CMV) differ depending on whether you have:
- primary CMV - where someone develops a CMV infection for the first time
- re-infection with CMV - an infection with a different strain of virus
- reoccurring CMV - a previously inactive CMV infection is reactivated, often because the immune system (the body’s natural defence against infection and illness) is weakened
- congenital CMV - a CMV infection develops when a woman is pregnant and infects the unborn baby

Primary CMV
Most cases of primary CMV cause no noticeable symptoms. If you do experience symptoms, they will be similar to flu symptoms and can include:
- a high temperature of 38C (100.4F) or above
- extreme tiredness
- sore throat
- swollen glands
- muscle and joint pain
- loss of appetite

These symptoms should only last for a couple of weeks.

Microbicide & Safe Sex (2)

STD Risk of unsafe sex
Vaginal or anal intercourse without a condom and/or microbicide — high risk for passing:
- chancroid
- chlamydia
- cytomegalovirus (CMV)
- genital warts
- gonorrhea
- hepatitis B
- herpes
- human immunodeficiency virus (HIV)
- human papilloma virus (HPV)
- pelvic inflammatory disease (PID)
- pubic lice
- scabies
- syphilis
- trichomoniasis

Oral sex without a condom — High risk for passing:
- CMV
- gonorrhea
- hepatitis B
- herpes
- syphilis

Microbicide & Safe Sex (1)

In this first decade of the 21st century the various risks connected with having sex have (alas) increased.
The figures for HIV, chlamydia and gonorrhoea are all going up. This is almost entirely because so many people – whether they're heterosexuals or homosexuals or 'bi' – don't practise safe sex.

One way to have safer sex is to only have one partner who has no sexually transmitted infections and no other partners than you.

But, this isn't always the safest kind of safer sex. That's because most people don't know when they have infections. They are very likely to pass them on without knowing it.

Another other reason is that some people aren't as honest as they should be. In fact, about 1 out of 3 people will say they don't have an infection when they know they do, just to have sex. So most of us have to find other ways to practice safer sex.

Another way to practice safer sex is to only have sex play that has no risk — or a lower risk — of passing STDs. This means no vaginal or anal intercourse. Many of us find that great sex is about a lot more than a penis going in a vagina or anus. It is about exploring the many other ways you and your partner can turn each other on. Not only is it a way to discover new sexual pleasures, it's also safer.

Safe Sex:
- Reduces our risk of getting a sexually transmitted disease (STD)
- Using condoms and/or microbicide makes vaginal or anal intercourse safer sex
Although condoms provide the best form of protection for people who are sexually active, using a microbicide will be much safer than nothing for women for whom condom use is unlikely or impossible.

For some women and men, the contraceptive effect of condoms is a major deterrent to use; developing both contraceptive and non-contraceptive microbicides is important. Providers can counsel patients on the use of microbicides in conjunction with condoms for added protection, and as a "backup" method when condom use cannot or does not occur.

Microbicide Delivery system

The past decade has seen several effective anti-HIV-1 agent discoveries, yet microbicides continue to disappoint clinically. Our review expounds the view that unsatisfactory microbicide failures may be a result of inefficient delivery systems employed.

Microbicide delivery devices will be critical in ensuring safe and effective use of microbicide products. The device impacts the product’s overall safety (relationship with product purity and stability, avoidance of local trauma associated with insertion or use), efficacy (consistent delivery of the required amount of product in the intended location), and acceptability (comfort, ease of use, disposability).

Several novel microbicide delivery methods to help reduce cost, ensure microbicide efficacy, and increase user acceptability. Methods include:
• Diaphragm:  This combination of barrier method and microbicide could enable prevention of both pregnancy and disease. Two studies were recently completed. One study assessed gel retention and distribution in the vagina comparing Diaphragm single-sided and double-sided gel delivery to a
vaginal applicator. The second study used the same three gel application modes and evaluated couples’ use acceptability.
• Paper applicator with dosage stop: This user-filled applicator is low cost, easily disposed of, and prevents over-filling, making it an important option for microbicide gel delivery in low-resource settings.
• Rectal applicator: This applicator has been designed specifically for the rectal delivery of microbicide products.

Intravaginal targeting of HIV-1 increases the chances of microbicide success, wherein vaginal micro environmental factors including pH should be maintained at HIV-1 prohibitive acidic levels simultaneously to ward off other sexually transmitted diseases, which compromise vaginal epithelial barrier properties.

Furthermore, choice of receptors to target both on HIV-1 and on target cells is vital in deterring transmission. Appropriate modeling of virus–target cell interactions as well as targeting early stages of the HIV-1 infection accompanied by computation and delivery of appropriate microbicide quantities could revolutionize microbicide research, ultimately delivering a female-controlled HIV-1 prevention modality appropriately.
(Qualitative and quantitative intravaginal targeting: Key to anti-HIV-1 microbicide delivery from test tube to In Vivo success; Viness Pillay,*, Felix Mashingaidze, Yahya E. Choonara, Lisa C. Du Toit, Eckhart Buchmann, Vinesh Maharaj, Valence M. K. Ndesendo, Pradeep Kumar)

More about Microbicides

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. Multiple compounds are being developed and tested for their microbicidal activity in clinical trials. Microbicides can be formulated in various delivery systems including gels, creams, lotions, aerosol sprays, tablets or films (which must be used near the time of sexual intercourse) and sponges and vaginal rings (or other devices that release the active ingredient(s) over a longer period). Some of these agents are being developed for vaginal application, and for rectal use by those engaging in anal sex.

Although there are many approaches to preventing sexually-transmitted diseases in general (and HIV in particular), current methods have not been sufficient to halt the spread of these diseases (particularly among women and people in less-developed nations. Sexual abstinence is not a realistic option for women who want to bear children, or who are at risk of sexual violence. In such situations, the use of microbicides could offer both primary protection (in the absence of condoms) and secondary protection (if a condom breaks or slips off during intercourse). It is hoped that microbicides may be safe and effective in reducing the risk of HIV transmission during sexual activity with an infected partner.

Journals Excerpts of Microbicide & HPV

About HPV
Human papillomavirus (HPV) is a virus from the papillomavirus family that is capable of infecting humans. Like all papillomaviruses, HPVs establish productive infections only in keratinocytes of the skin or mucous membranes.

While the majority of the known types of HPV cause no symptoms in most people, some types can cause warts (verrucae), while others can – in a minority of cases – lead to cancers of the cervix, vulva, vagina, penis, oropharynx and anus. Recently, HPV has been linked with an increased risk of cardiovascular disease.In addition, HPV 16 and 18 infections are strongly associated with an increased odds ratio of developing orophanyngeal cancer.

More than 30 to 40 types of HPV are typically transmitted through sexual contact and infect the anogenital region. Some sexually transmitted HPV types may cause genital warts. Persistent infection with "high-risk" HPV types — different from the ones that cause skin warts — may progress to precancerous lesions and invasive cancer. HPV infection is a cause of nearly all cases of cervical cancer. However, most infections with these types do not cause disease.

Microbicide & HPV
HIV-1, herpes simplex virus type 2 (HSV-2), and human papillomavirus (HPV), among other sexually transmitted infections, represent a major burden for global health. Initial insights into the mucosal transmission of these viral pathogens have raised optimism with regard to the rapid generation of protective vaccines. Nevertheless, setbacks for HIV-1 and HSV-2 vaccines have seriously challenged the initial enthusiasm.

Recently, two new vaccines that efficiently prevented HPV infection have renewed the hope that vaccinal prevention of viral mucosal sexually transmitted infections is possible. HIV-1 and HSV-2 differ from HPV, and each virus needs to be tackled with a distinct approach. However, vaccines are not the only possible answer. Topically applied agents (microbicides) are an attractive alternative in the prevention of HIV-1 and HSV-2 mucosal transmission. Progress in understanding the mechanisms of genital transmission of HIV-1 and HSV-2 is required for successful vaccine or microbicide candidates to emerge from current approaches.
(Vaccines and microbicides preventing HIV-1, HSV-2, and HPV mucosal transmission; Nikolic DS, Piguet V.)

Microbicide & STD

What Does Everyone Need to Know About STDs?

Sexually transmitted infections (STI), also previously referred to as sexually transmitted diseases (STD) and venereal diseases (VD), are illnesses that have a significant probability of transmission between humans by means of human sexual behavior, including vaginal intercourse, oral sex, and anal sex. While in the past, these illnesses have mostly been referred to as STDs or VD, in recent years the term sexually transmitted infections (STIs) has been preferred, as it has a broader range of meaning; a person may be infected, and may potentially infect others, without having a disease. Some STIs can also be transmitted via the use of IV drug needles after its use by an infected person, as well as through childbirth or breastfeeding. Sexually transmitted infections have been well known for hundreds of years.

Everyone, young or old, rich or poor, sexually active or not, needs to know a few important facts about sexually transmitted diseases. It’s particularly important that, if we are parents, we spend time throughout our children’s lives discussing these issues in an age-appropriate manner. The more educated our children and teens are about the facts about sexually transmitted diseases, the better the chance is that if they do decide to have sex they will know how to protect themselves from sexually transmitted diseases and infections, as well as HIV the virus that causes AIDS, and unplanned pregnancy.

Sexually transmitted diseases do not discriminate. You can be any age, race, religion, financially secure or insecure, any education level and hold any job from blue collar to CEO. The point is anyone who participates in sexual activity is at risk of contracting a sexually transmitted disease or infection.

It may not surprise you to know that the majority – two-thirds – of all sexually transmitted diseases occur in teenagers and young adults under the age of twenty-five years old. Even with all the education and resources available today, sadly, the number of cases of STDs continues to rise.

Some ways to reduce the chance of having sexual contact with a member of the infected pool, and thus of becoming part of that pool include:

- Stop having sex until you see a doctor and are treated.
- Follow your doctor's instructions for treatment.
- Use condoms and/or microbicide whenever you have sex, especially with new partners.
- Don't resume having sex unless your doctor says it's OK.
- Return to your doctor to get rechecked.
- Be sure your sex partner or partners also are treated.

Microbicide & Herpes (2)

Genital herpes is one of the most prevalent sexually transmitted infections worldwide and is the most common cause of genital ulcers. Despite increased public awareness and the initiation of efforts to prevent transmission, the prevalence of herpes simplex virus (HSV) type 2 continues to increase.

What makes HSV so difficult to control is that most sexual and perinatal transmission occurs during unrecognized or asymptomatic shedding. The impact of genital herpes as a public health threat is amplified because of its epidemiological synergy with HIV/AIDS. Thus, there is an urgent need for novel prophylactic methods, such as topical microbicides designed for genital application, to prevent both HSV and HIV transmission.

In summary, genital herpes is a critical global health priority because of its devastating impact on young adults and infants and its association with the HIV/AIDS epidemic. Topical microbicides that block transmission at the mucosal surface may provide a realistic method of intervention for worldwide distribution. Currently, there are several candidate drugs being advanced to clinical trials that block both HSV and HIV infection by inhibiting binding and entry in vitro.

Whether blockade of entry will be sufficient to prevent sexual transmission or whether a combination strategy targeting multiple steps in the viral life cycle will be required is not yet known. Importantly, before embarking on large-scale clinical trials, more extensive evaluation of candidate microbicides, including assessment of the impact on innate defences, is warranted. Assessment of the safety and mucosal response to microbicides should be accrued from several different models including cell and organ cultures, animal models and, most importantly, pilot clinical studies.

((Excerpt of)Topical microbicides for the prevention of genital herpes infection: Marla J. Keller, Ana Tuyama, Maria Josefina Carlucci and Betsy C. Herold)

A topical microbicide that silences two genes can safely protect against genital herpes infection for as long as one week, according to a joint study by researchers at the Albert Einstein College of Medicine of Yeshiva University and Harvard Medical School.

Microbicide & Herpes (1)

Excitement here over a microbicide that protects women against HIV grew when researchers reported that it also protects against herpes simplex virus-2 (HSV-2) infection.
The gel is not a contraceptive, but a microbicide. Microbicidal gels or creams are inserted into the vagina solely to prevent the spread of HIV and other sexually transmitted diseases. There are currently no such products on the market. Women who have herpes are at increased risk of contracting HIV, so diminishing the risk of getting herpes also diminishes the risk of HIV infection.
In a randomized controlled trial, the vaginal gel reduced women's risk of HIV infection by 39% compared with placebo, according to researchers.


A 2010 clinical trial found that microbicides -- vaginal gel spiked with antiretrovirals -- cut HIV transmission during sex by 39 percent. But researchers also found that microbicides reduced a woman's risk of herpes by a whopping 51 percent.

(Excerpts of) A Summary of Preclinical Topical Microbicide Vaginal Safety and Chlamydial Efficacy Evaluations in a Pigtailed Macaque Model

Patton, Dorothy L. PhD; Cosgrove Sweeney, Yvonne T. BA; Paul, Kathleen J. MPH

Background:
The development of topical microbicides represents a new and exciting field in the prevention of sexually transmitted diseases, and it is especially important that candidate products undergo rigorous preclinical safety and efficacy testing before advancing to clinical trials.

Methods:
We have developed a standardized protocol for preclinical vaginal safety and efficacy assessment of topical microbicide candidates in a nonhuman primate model. Over 7 years of funding under an NIH contract, we evaluated a total of 28 test compounds for vaginal safety (via colposcopy, vaginal pH, and microflora) and 9 compounds for efficacy against cervical chlamydial infection. We also outline the specific criteria used to determine which products should move into efficacy trials and which should be recommended for reformulation to the manufacturer.

Results:
Overall, we noted acceptable safety profiles for 24 of 28 candidate products. Common findings included a transient decrease in vaginal pH, petechiae, and mild erythema. Four products were associated with significant adverse colposcopic findings including blisters, epithelial abrasions, and friability; all 4 products were successfully reformulated and showed acceptable safety profiles at lower concentrations. No products showed complete protection against cervical chlamydial infection.

Conclusions:
The macaque preclinical safety and efficacy model is critical to maintaining the pace of topical microbicide development, which could ultimately offer a significant opportunity for intervention in the global HIV/AIDS epidemic.

Overall safety profiles were acceptable in 24 products. Microbiologic findings common to most products included stable populations of H2O2-producing lactobacilli and Viridans streptococci and transient decreases in anaerobic Gram-negative rods.

Microbicide Safety

The development of topical microbicides represents a new and exciting field in the prevention of sexually transmitted diseases, and it is especially important that candidate products undergo rigorous preclinical safety and efficacy testing before advancing to clinical trials.


The physico-chemical and biological properties of active pharmaceutical ingredients (APIs) and their formulations are the foundation of safe, efficacious and acceptable microbicides. Hence, the initial selection of the API and its primary formulation is crucial. Certain undesirable properties of an API can be compensated or masked by an appropriate formulation. However, there is a risk in proceeding with inadequate APIs or formulations, as they may fail later in development, costing more time and money. 

It is important to have a set of criteria that inform Go/No Go decisions prior to entering in clinical trials. This set of criteria is based on API and formulation parameters derived from a comprehensive evaluation of their in vitro P/C properties, drug release rates, specific activity, and cell and tissue toxicity, which in turn represent the base for animal studies focused on organ toxicity/safety, pharmacokinetics (PK), and pharmacodynamics (PD) and efficacy.

A solid preclinical foundation will help navigate clinical testing successfully, ultimately leading to a safe and effective microbicide. In addition to the more classical IND-enabling studies, new models, assays and biomarkers have been developed and adapted to the evaluation of genital and rectal microbicides.

Experience with previous microbicide candidates has led to the inclusion of assays evaluating the impact of genital environmental factors such as low pH, seminal plasma, CV secretions and microflora on microbicide safety and efficacy. Microbicide-induced inflammatory mediators and alteration of innate immunity have also been recently incorporated to the standard testing.

Looking for a Few Good Microbicides Candidates

Until recently, microbicide discovery was a by-product of the search for anti-HIV drugs. Early in the search for microbicides, for example, attention focused on detergents because of their ability to disrupt HIV’s coat. Most such easily testable candidates, however, failed as microbicides. Now that scientists know more about HIV’s life cycle,
they are beginning to identify multiple points at which the virus could be stopped.

Ideally, a microbicide should be:
• Colorless and odorless
• Inexpensive to manufacture and purchase
• Safe to use more than once a day and for long periods of time
• Effective against multiple STDs, including HIV/AIDS
• Fast-acting, long-lasting, and non-irritating
• Undetectable to either partner
• Available in contraceptive and non-contraceptive forms
• Available without a prescription

In theory, creating an effective topical microbicide should be easy. Simply identify chemicals that kill disease-causing organisms, blend the chemicals with an inert gel or foam, and place it in the vagina. Experience, however, has shown that the simple approach may not work.

The Research Pipeline 
Like a new drug or vaccine, topical microbicide development will follow a pathway—the research pipeline—from basic research to commercial production. The key points along the pipeline are basic research, product formulation and preclinical testing, and clinical testing.

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.