Research funding of £90m is to be directed towards British researchers to develop a gel which will “stop HIV/Aids in its tracks” reported The Times. It is hoped the funding by the UK government and the Bill and Melinda Gates Foundation will lead to a gel that could be applied before sex to prevent transmission of the HIV virus. A gel of this type is important as it would allow women to apply their own protection rather than relying on a partner to use a condom.
Earlier this month scientists announced the results of a trial looking at the safety and effectiveness of two gels. Between February 2005 and September 2008 women in several African countries and Philadelphia in the US were asked to use the gels and one was associated with reduced transmission rates. The encouraging signs of success from this early trial have led to optimism that these gels may offer better HIV control than vaccines, which have proved difficult to develop.
The Times quoted Professor Robin Shattock, chairman of a scientific advisory board on microbicides, as saying that, in the past, microbicides were not taken seriously, but they could have a role now that “vaccines may not deliver in the timeframe previously promised”.
Generally, the term microbicide may refer to any compound whose purpose is to reduce the infectivity of microbes, such as viruses or bacteria. Microbicides, when used to prevent the sexual transmission of HIV and other sexually transmitted infections, are usually gels, foams or creams applied topically inside the vagina or rectum.
There are three main ways HIV can be transmitted: sexual transmission, transmission through blood and mother-to-child transmission. All strategies aiming at prevention rely on increasing awareness of what works, through mass media campaigns and education in schools combined with more directed campaigns for key groups such as men who have sex with men, injecting drug users and sex workers. The proposed method of reducing sexual transmission has, up to now, been through the use of condoms.
For transmission through blood and blood products, needle exchange programmes for injecting drug users have been shown to reduce the number of new HIV infections without encouraging drug use. The safety of activities that involve blood contact, such as tattooing, can be improved by routinely sterilising equipment.
Mother-to-child transmission during pregnancy, labour, delivery and breastfeeding can be reduced by antenatal screening to identify HIV positive women and the use of antiretroviral drugs, safer infant feeding practices and other interventions, such as caesarean section, for delivery.
Most HIV-infected women become infected through sexual intercourse with an infected male partner. Although condom use is the main way to prevent sexual transmission applying gels and cream is a prevention method women could initiate themselves. This would be particularly helpful in situations where it is difficult or impossible for women to refuse sex, negotiate condom use with their male partners or in areas where reliable condoms may not be readily available.
On February 9 the US National Institutes of Health (NIH) released its report on the HPTN 035 trial. This was a phase II/IIb clinical trial which enrolled more than 3,000 women, and was the NIH’s first large clinical study of a microbicide for preventing the transmission of HIV.
The trial was designed to test the safety and preliminary effectiveness of two microbicide gels, PRO 2000 at 0.5% dose (manufactured by Indevus Pharmaceuticals) and BufferGel (manufactured by ReProtect Inc.). The researchers also tested a placebo gel in a group of control women prior to engaging in sexual intercourse and also compared the HIV infection rates in a group of women who did not use any gels before engaging in sexual intercourse. This last group was included as it was thought that even using an inactive gel might provide a small level of protection.
It found that use of PRO 2000 was safe and approximately 30% effective, though this was not statistically significant. Of 194 women in the study who became infected with HIV 36 were in the PRO 2000 group, 54 in the BufferGel group, 51 in the placebo gel group and 53 among those who did not use gel. Although these differences were not statistically significant, a trend was demonstrated. It may be that a larger, phase III trial recruiting more women could demonstrate a significant benefit.
The authors conclude that the PRO 2000 gel may prevent male-to-female sexual transmission of HIV infection and that it shows promise. The BufferGel had no detectable effect on preventing HIV infection.
Medication that relies on repeat applications by an individual may be less effective if not applied correctly or frequently enough. There may also be differences in how conscientiously women use the gel in clinical trials compared to in real life. During the trial, both microbicides were found to be well tolerated and did not result in any significant adverse events.
There was good compliance in this trial, suggesting that the gels were easy to use. Almost all women (94%) completed the trial. The women used the gels regularly (81% of sex acts), and nearly all women (99%) said they would use the products if they were approved for HIV prevention. Condom usage was also high throughout the course of the trial (72%).
Commentators have compared the potential effectiveness of these microbicidal gels to the potential effectiveness of vaccines, saying that although the gels could be the key to HIV control now they will never have the “blanket disease-eradication power” of a vaccine, which is yet to be developed.
There are other microbicide studies yet to report their findings, including a separate clinical study sponsored by the Medical Research Council and the Department for International Development of the United Kingdom. This is a phase III clinical study involving nearly 9,400 women, and is set to conclude in August 2009. It is also testing PRO 2000 (0.5% dose) in preventing HIV infection among women in Africa, and is expected to provide additional information about the microbicide’s effectiveness.