Kigali — In the wake of last month's unexpected closure of Phase III clinical trials of Cellulose Sulfate (CS), Rwanda-based microbicide researchers have assured the public that the development did not mean a similar fate for other ongoing microbicide studies.

According to Projet Ubuzima, an international non-profit making research project carrying out clinical trials on Dapirivine gel - another microbicide product - in Rwanda, the halting of CS clinical trials has no bearing on other related research work.

"The news about the closure of cellulose sulphate is disappointing and unexpected but does not mean that microbicide development should stop. Drug development always involves many failures before one success and in this case, when we do eventually have success, this will save millions of lives," the project said in a statement last week.

CONRAD, a US-based reproductive health research organisation on January 31, announced it had stopped clinical trials of CS - a topical microbicide gel being tested for HIV prevention in women -"because preliminary results indicated that cellulose sulphate could lead to an increased risk of HIV infection in women who use the compound."

The Phase III study which began in July 2005 was being conducted in South Africa, Benin, Uganda and India involving 1,300 women. Phase III tests are at the level of efficacy trials, which is the final laboratory analysis to determine to effectiveness of a drug

In Rwanda, researchers at Projet Ubuzima are in the final stages of Phases I and II, which seek to determine the safety and acceptability (especially among women) of Dapirivine gel.

SC is a first generation microbicide, whereas Dapirivine is belongs to the second generation. Dr Eveline Geubbles, the scientific manager at Projet Ubuzima, told The New Times last week that microbicide clinical trials in Kigali remained on track despite the disappointing results in the CONRAD CS trials.

She expressed confidence that current safety trials on Dapirivine gel would give positive results, marking a major step in microbicide research in the country.

"Currently, we are the stage of data analysis. We sent the data (to the US) for laboratory tests and we expect results around the end of this year," Geubbles said from the project's offices in the posh Kiyovu suburb, Nyarugenge District.

The research was conducted on 28 HIV-negative Rwandan women who volunteered to assist in the Dapirivine research, which is also underway in Tanzania and South Africa.

Prior to the research, the women underwent thorough medical tests to detect any Aids, liver and kidney viruses; and were asked whether they felt any other bodily complications to ensure that proper data was collected, explained Geubbles.

In Rwanda, the study was first done on rabbits and mice before being applied to humans, she added.

Besides, the halting of the Phase III efficacy trial of cellulose sulphate by CONRAD, another related but different microbicide clinical trial by Family Health International (FHI) was also stopped in Nigeria. This particular trial involved 1,644 women.

"Although the FHI trial has not detected an increased HIV risk associated with cellulose sulphate, FHI made the decision as a precautionary measure, given the preliminary results in the CONRAD trial," CONRAD, a cooperating agency of the US Aid for International Development said in a statement.

There are several clinical trials going on in about 20 countries worldwide to try and find a microbicide (a chemical that will kill microbes - in this case HIV the virus) that can protect women by applying it in the vagina before sex.

No scientific explanation

In the CONRAD CS trial, it was found out that women who were given the microbicide gel to use did not get any protection from it compared to the control group that did not use the gel.

Researchers also feared that the gel may have put some of the volunteers (the women who applied it) in danger of HIV infection.

There was no immediate scientific explanation to the collapse of CS trial, but experts from the Independent Data Monitoring Committee (IDMC), an independent advisory group that was overseeing the trial, said they will conduct a detailed review of the data to better understand the findings. The experts will also help determine any implications for other microbicide studies, CONRAD said.

"This is something that has been feared from the very beginning of mocrobicide research - that whatever chemical is used, it must not damage the vaginal lining (and make it more prone to viral entry) while killing the virus," a renowned Zambian Aids activist Dr Manasseh Phiri, said.

At the moment, microbicides are still in the form of a gel, cream and thin films, but it is expected that if current efficacy studies succeed, microbicides will eventually be availed in the form of a tablet, sponge or a vaginal ring with the capacity to release active ingredient against invading viruses.

The microbicide field will now wait until around the end of 2007 for the first ever microbicide efficacy results, to determine the future of the much hyped-clinical tests for various products of microbicides. This particular study underway in South Africa is in its Phase III trial stage, and seeks to determine the effectiveness of carraguard gel, a first generation microbicide.

At the moment, Projet Ubuzima, an organisation bringing together researchers from Rwanda, The Netherlands and the US, is implementing a study to measure the incidence of HIV in high-risk women and female Voluntary Counselling and Testing (VCT) clients.

This ongoing research is conducted on a group of prostitutes who have no plans of quitting the practice. This trial, according to Geubbles, is aimed at determining the efficiency of Dapirivine in future trials.

Asked whether there is hope for any breakthrough in the microbicide studies, Geubbles said: "That is what we hope for. Research is like a baby who tries to walk, then falls, and then, keep on trying until he or she finally makes it."

Magic bullet

She however explained that even after the studies give positive results, microbicides will not replace the present preventative measures against HIV, but will just supplement abstinence, faithfulness and condoms - current preventive tools.

"Micribicides will not be a magic bullet. It is not going to be a 100 percent effective," she said.

Scientists estimate that if microbicides become effective and are used by about 20 percent of women at high risk, they will protect at least 2.5 million infections in three years in Africa, South America and Asia.

Studies indicate that the first generation microbicides are only likely to be 40% to 60% protective against HIV, whereas second generation microbicides would be between 60% and 80% effective.

The first generation microbicides only increase the rate of acidity in the vagina hence more immunity, while the second generation microbicides have the added value of an ARV component, making the vagina even more resistant against infections.

Microbicides have received formidable support from governments, international activists and philanthropies who want to put protective products in the hands of women who are more vulnerable to the HIV pandemic.

Leading the pack in supporting microbicide research is the Bill and Melinda Gates Foundation, (owned by Microsoft's founder and world's richest man, Bill Gates, investing a staggering $125 million, including $12 million for the closed CONRAD trial.