Enlisting microbicides in the fight against HIV/AIDS

Sir Gustav Nossal writes that Australian scientists are at the vanguard of developing what could be the most effective weapons in the battle against one of the deadliest of diseases. Despite our growing knowledge of the biology of HIV, the spread of infection and subsequent development of AIDS continue apace. Clearly, HIV is a vicious enemy which must be attacked on a large number of fronts if we are to halt the continued spread.

Slowing the rate of HIV infection is not a simple matter of developing a drug or vaccine on the one hand, or promoting safe sex or abstinence on the other. The pharmaceutical approach is problematic and slow at best, and changes in behaviour are difficult to achieve for a number of reasons. The effective approach is likely to be one that pulls out all stops.

One of the problems with developing a vaccine against HIV/AIDS is also a feature of research into a vaccine for malaria and flu -- the infective agents for each of these diseases is readily able to 'change its spots' and does so frequently, thereby dodging the immune attack.

But HIV has an extra, deadly weapon in its arsenal that presents a unique problem -- the virus attacks the very cells of the immune systems that would otherwise defend the body, as a result of which it is extremely difficult to deliver the vaccine.

Despite the problems, there has certainly been progress toward an HIV vaccine. An AIDS-like illness can be controlled in non-human primates by a vaccine process called 'prime-boost' in which one variant of the virus is injected to prime the immune system and a second variant is used later to boost the immune response.

However, more than 50 trials of vaccines in humans, costing billions of dollars, have failed. A preventive vaccine remains a long way from reality. The development of antiviral drugs effective against HIV has been far more successful and Melbourne company Avexa currently has a new antiviral in clinical trials. In fact, the first registered vaccine may be therapeutic rather than preventive, capable of decreasing the viral load in people who have already been infected with HIV. The concentration of viral particles in blood is the best prognosis for progression to AIDS. Low levels are associated with 10 to 15 symptom-free years and at higher levels, this 'healthy' period is decreased. Australian Company Virax is one company with a therapeutic vaccine in clinical development.

The lack of empowerment of women in regions where HIV infection is widespread, such as parts of Asia and Africa, is a major obstacle in the battle against HIV/AIDS. In countries where infection rates are the highest, women are often subjugated and lack basic rights. It is of little consequence that a woman may have received the safe sex message and demand the use of condoms if her male partner refuses her request. In the context of empowering women, there are two choices. One of these is the female condom, a polyurethane sheath that presents a physical barrier to sperm and sexually transmitted infection. The female condom is far from a perfect solution. It is prone to human error, has a high failure rate and is difficult to use.

The second choice is a vaginal microbicide, an agent applied to the vagina before intercourse that prevents viruses and bacteria from taking hold. Such an agent has tremendous potential in preventing the spread of HIV as well as other sexually transmitted infections such as genital herpes, a disease which itself increases the incidence of HIV infection. Microbicides may also be useful for birth control, through spermicidal or sperm immobilising action.

Australian scientists are at the vanguard of microbicide development. There is a microbicidal gel being developed by the Australian company, Starpharma, for the prevention of sexually transmitted infections such as genital herpes and HIV. To date, this product has passed all developmental hurdles with flying colours. The next steps will involve rigorous clinical development and, ultimately, translation to the field.

A second strength relates to the concept of nanotechnology in medicine. Starpharma's microbicide may be one of the first nanopharmaceutical drugs to satisfy all regulatory requirements from agencies such as the US Food and Drug Administration and reach the clinic. An extraordinary achievement in itself, such an outcome will also carry considerable symbolic value.

Starpharma and many other Australian companies and research organisations are perfect examples of Australian scientists mixing it with the best in the world. The company was established as a spin-off from Australian academic science and technology, based on an idea conceived at the CSIRO. Starpharma's microbicide has also been amply supported financially by the National Institutes of Health in the US to accelerate its development.

The first nanotechnology-based microbicide is well on the way to clinical reality. The fight against HIV stands to benefit greatly from attainment of this goal.