Microbicides

9.1 Overview

Women are disproportionately affected by the HIV/AIDS epidemic in Africa. According to a UNAIDS Africa Factsheet (2005), in Sub-Saharan Africa 57% of those infected with the virus are female, or approximately 17-million women and girls. In Sub-Saharan Africa, 77% of the almost 9-million HIV-positive youth (15-25) are female.

The reasons for this are outlined in the gender factsheet. They include a biological vulnerability (heterosexual women can far more easily become infected through penetrative sex than heterosexual men) and a socio-economic vulnerability (women are often economically dependent on their husbands or partners). Women are often unable to negotiate condom use or other protective measures with their partners.

Microbicides, though not widely available yet, have the potential to provide a discreet method for women to protect themselves against HIV infection. Some microbicides can also be used as contraceptives.

9.2 Definition

A microbicide has the capacity to kill, neutralise or block HIV and STI infection.

9.3 How Do Microbicides Work?

Microbicides can prevent HIV infection in any one of the following ways:

• By killing pathogens by breaking down the surface of the germ
• By strengthening the body's normal defences
• By inhibiting viral replication
• By inhibiting viral entry and binding of viruses to healthy cells

9.4 Benefits for People Already HIV-Infected

Microbicides will help to reduce the risk of re-infection for HIV-positive people and protect HIV-negative partners from HIV-infection. They will also help reduce the transmission of other sexually transmitted infections. Microbicides are able to allow for conception while protecting both parties from STIs.

It is important to note that microbicides are aimed to be used alongside condoms and should not replace condoms completely.

9.5 Research and Clinical Trials

Microbicides are not available to the public yet, but are projected to be released into the health sector in South Africa by 2007. To date, almost all research has been done by non-profit organisations, universities and small biotech firms.

Research has produced almost 60 products, which are poised for further testing. Phase 3 trials are conducted by comparing two groups — those who receive the microbicide trial plus a standard prevention package and those who receive the prevention package plus a placebo gel. The placebo gel looks identical to the drug being studied, but doesn't contain the active ingredient.

All participants receive intensive condom counselling, free high-quality condoms and regular treatments for STDs. It normally takes about ten years for a product to develop into a fully tested product.

The three products which are among the closest to public release are:

Carraguard (PC-515)

Carraguard is a clear gel derived from seaweed, and it works by blocking the attachment of pathogens to target cells. It is effective against HIV, HSV-2, and gonorrhoea in vitro. It is currently undergoing phase 3 trials in South Africa and Botswana. Enrolment began in March 2004 in Pretoria, Cape Town and Durban. Carraguard does not require refrigeration and can still retain effectiveness following lengthy storage. It does not have contraceptive properties.

PRO-2000/5

This is a naphthalene sulfonate polymer, and blocks attachment of pathogens to target cells. It is active against HIV-1 in vitro (in an artificial environment, e.g. test tube) and against HIV-1 and HSV-2 in vivo (in the body). PRO-2000/5 does, however, have contraceptive properties, when tested in animals. It works by preventing any virus from entering the uterus. It has also shown effectiveness against multiple STD organisms. It is still in Phase 2/2b trials. Enrolment began in February 2005. Three thousand participants enrolled in Durban and Hlabisa, South Africa; Lilongwe and Blantyre, Malawi; Moshi, Tanzania; Philedelphia,USA; Lusaka, Zambia; Harare and Chitungwiza, Zimbabwe.

Buffer Gel (Carbomer 974P)

This is an aqueous gel, which employs an agent which is widely used in pharmaceuticals and which helps maintain the vagina's natural acidity in the presence of sperm. Buffer gel is used in the manufacture of lipsticks, hand lotion and vaginal lubricants. This compound inhibits HIV, genital herpes, chlamydia, HVP and gonorrhoea. Enrolment trials began in February 2005 with 3000 participants from South Africa, Malawi, Tanzania, Philadelphia, Zambia and Zimbabwe.

9.6 Distribution

Ideally, microbicides should be available at the same places condoms are commonly found:

• government health and family planning clinics
• pharmacies
• community-based distributors and through village health workers
• local shops, beauty parlours, taxi stands, markets and convenience stores
• youth organisations, women's groups and through sex workers

A number of characteristics have to be considered such as bio-stability, shelf life, and storage requirements. Health-care clinics, pharmacies and various health programs will be routes for distributing both prescription and over-the counter (OTC) products. In this way, education, counselling and support for potential users can be provided.

Several studies have shown that women and men would like to obtain microbicides through the formal health system.

9.7 Microbicide Reliability and Acceptability

For a microbicide to be acceptable, it has to fill the following criteria:

• be safe,
• be available over the counter
• be affordable
• be odourless
• be easy to apply
• not interfere with sexual pleasure
• allow for application several times during intercourse

The first generation of microbicides to reach the market are expected to be 50-60% effective in preventing HIV infection, with the protection rate going up to 80-90% by the third generation as products are improved. If microbicides are to have any impact at all on the HIV/AIDS epidemic, they have to be accessible to girls and women who are at the highest risk of contracting HIV. There has been concern, however, that in certain circumstances such as "dry sex", and where cleaning and drying agents are used, microbicides may not be as acceptable.

Even with these concerns, microbicide use and acceptability has varied. Evidence collected from countries such as Belgium, Brazil, Thailand, South Africa, Uganda, UK, US and Zimbabwe suggest the following:

• Women in a variety of settings express a high level of interest in microbicides
• Safety and effectiveness remains a priority
• The effect on sexual pleasure is another consideration

Before microbicides are actually introduced, a framework will have to be developed for their introduction, promotion and delivery. The sooner this occurs, the better prepared policy makers will be for reaching decisions about the adoption of microbicides.

9.8 The South African Context

In South Africa, a research study conducted by International Family Health, found:

• A relatively low efficacy microbicide could still impact on a high-incidence area such as Hillbrow for instance.
• A microbicide of 40% HIV and STI efficacy can reduce HIV incidence by 9% if it is used by 75% of the population in 50% of non-condom protected acts. This also assumes that microbicide users reduce their level of condom use by 5% (a 5% condom migration).
• The degree of impact achieved is determined by the level of distribution of the microbicide — at low distribution levels, microbicides will still avert HIV infections, but will not greatly affect the evolution of the epidemic.
• The earlier microbicides are introduced, the larger the impact they could make on the millions of new HIV infections.