Kampala — UGANDAN scientists have defended HIV/Aids vaccine tests on human beings even after a female-friendly microbicide gel trial was stopped recently because women using it got infected at an almost similar pace as those not using it.

Prof. Florence Mirembe, a lead investigator at the Mulago-based Microbicides Centre in Kampala, said that the 1,333 women who participated in the failed trial were counselled and educated on the intentions of the research and informed of the possibility of HIV infection.

The women were drawn from Uganda, Benin, Burkina Faso, South Africa, Nigeria, and India. Dr Mirembe, who also is a professor of obstetrics and gynaecology at Makerere University Medical School, declined to reveal the number of Ugandan women who were involved in the failed trial.

Prof. Mirembe led the investigation in Uganda while other researchers did the same in the different countries. The women involved in the trial were divided in two groups. One group used the gel that contained cellulose sulphate - the name of the microbicide that was being tested - while the other group used the gel without the microbicide.

At the end of the 12-month trial, 34 women of the 1,333 from across the participating countries became infected with HIV, the virus that leads to Aids. Some 23 of the 34 infected women used the gel with the cellulose sulphate and 11 used the gel without the sulphate.

In an earlier interview with Daily Monitor, Prof. Mirembe hinted that the women involved in the trials would not be compensated if they got infected because they had already signed consent agreements and that this was just a trial. It is also not clear whether they will be treated.

According to the World Health Organisation, microbicides are compounds that can be applied inside the vagina or rectum to protect against sexually transmitted infections including HIV. They can be formulated as gels, creams, films, or suppositories.

The microbicide gel that was being tested, according to Prof. Mirembe, is a substance that was designed for women to apply in the vagina before sexual intercourse to prevent catching HIV and other sexually transmitted infections.

Conduct of trial

Prof. Mirembe said that the women involved were educated about the dangers involved in the trials. "At the first visit, we send the women back home so that they can think about the whole trial," she said. "If they want to participate, then they can come back."

Those who returned and accepted to be part of the trial were screened to ensure that they did not have any sexually transmitted infections including HIV/Aids. The women also signed consent agreements before participating.

"We gave them the consent forms which they would read, internalise and return within 28 days from the day they had been screened and those who accepted the terms came back to us voluntarily," Prof. Mirembe said.

When the women returned, those who accepted to be part of the trial were re-screened.

Throughout the period of the trial, the women were encouraged to use the condom and the gel concurrently.

They were also screened and monitored every three months for the 12-month trial period to ensure that they complied with the guidelines. Dr Clementina Nakabiito, a co-investigator, said the women knew what they would go through. "They are given a list of expectations before taking part in the trials," she said. Dr Nakabiito said that there are regulations governing all clinical trials to protect volunteers. "We also have committees in place that monitor these trials to ensure no breach of contract between the volunteers and the people carrying out the trials," she said.

Prof. Mirembe said Researchers found that the substance [cellulose sulphate] was not making any difference. "The number of women using the gel [with the microbicide] got infected at the same rate with those who did not use it.

As a result there was no need to continue with the trial. The substance was safe but not effective. This is like any other drug [trial]. If found ineffective, you abandon it.

"It is not the substance gel that was infecting the women but the general sexual behaviour. The emphasis was on condom use, and we provided condoms for free so that the women could use the condoms together with the gel."

In a country where women are increasingly becoming infected with HIV/Aids at a higher rate than men, Prof. Mirembe said a more female-friendly preventive measure is necessary.

She said the Aids epidemic is no longer occurring among risk groups only. In fact, new infections are occurring through sexual transmission and especially among married women. "Married women are at a greater risk," the medic said. "It is not true that by virtue of being married they are more protected. Sexual intercourse remains the major cause of infection."

Although estimates put the number of people living with HIV/Aids in the world at about 40 million, Prof. Mirembe believes what is actually on the ground is not known.

More than 20 years into the epidemic, the latest Uganda HIV/Aids Sero-behavioural Survey indicates that 7.9 percent of women have HIV/Aids compared to 6 percent in men.

Globally, the trend is not any different. According to the 2006 Joint United Nations Programme on HIV/Aids report, more than 50 percent of 40 million people living with HIV worldwide are women. Although condoms have been widely used as a preventive measure, they are not completely effective.

"It is only abstinence that is totally effective but married women cannot dictate how and when to use condoms," Prof. Mirembe said. "This is why we wanted some kind of a women-friendly measure."

Women role matters

Although Uganda has received international acclaim as a model country in the fight against HIV/Aids, having cut prevalence from about 30 percent in the early 1990s to about 7 percent today, health experts say a further reduction in prevalence will require a combination of preventive strategies that include women-friendly interventions.

Dr Hannah Kibuuka of the Makerere University Walter Reed Project says in a paper on updates and gender issues related to HIV vaccine research that women are more vulnerable to HIV/Aids because of social, cultural, economic, and legal reasons.

"All these factors create unequal balance of power between men and women leading to differential risk to HIV and have an implication for the conduct of HIV trials in developing countries," Dr Kibuuka writes. According to her, behavioural approaches are particularly difficult for women.

"Female initiated and controlled prevention options are imperative because they increase available choices and provide opportunities for control of women's decisions," Dr Kibuuka says in the paper.

She adds that the gender issues that increase women's vulnerability to HIV/Aids may still work to prevent access and use of new preventive technologies. Giving trends of enrolment for HIV/Aids vaccine trials in Uganda since 1999, Dr Kibuuka says women participation has been very low.

For example, phase I trials between 1999-2005 indicate that enrolment for trials was at an average of 80 percent men compared to only 15 percent women while in phase II trials between 2005-2007, 70 percent of the enrolled volunteers are male compared to 35 percent female. Dr Kibuuka says female enrolment in vaccine trials should be encouraged so that researchers can establish how particular vaccines could work in men and women.

Dr Kibuuka writes in her paper: "The main potential barriers to women's participation in vaccine trials include lack of autonomy to make independent decisions about HIV testing, fear of contracting the virus and effect of the vaccine on future pregnancies. "A requirement to avoid pregnancy during the trial is a constraint in cultures where a woman's worth is linked to her fertility."

Other trials

The search for an HIV/Aids vaccine in Uganda has been ongoing since 1999 when the International Aids Vaccine Initiative and the Joint Clinical Research Centre first took the step to finding a solution to HIV/Aids.

Currently, three major players are involved in clinical trials in Uganda for a vaccine: The Makerere University Johns Hopkins University Project, Makerere University Walter Reed Project and the International Aids Vaccine Initiative.

Besides these trials, there are ongoing trials in more than 20 countries, especially in Africa and Asia where a majority of new infections are occurring. Although the microbicide trials have been halted, Prof. Mirembe said it was a good research and a great opportunity for the women.

"Some of the women had never consulted a medical practitioner or heard of a gynaecologist. Yes, we lost a battle as per this particular trial but the research will help us in finding other products."

Testing on humans

Concerns have also been raised over what stage human beings can be subjected to tests while developing new drugs or vaccines and the risks involved. According to Prof. Mirembe, the process of developing a vaccine is drawn out with extensive trials on animals before human beings come in.

"We start with rats, go to monkeys, rabbits, chimpanzees and ultimately humans," she said. "If the drug passes those stages in animals and shows positive response, we then start the trials in human beings."

Prof. Mirembe, however, said this is not a guarantee that if it is tested on people, then it is effective. At the human level, the trial will also take three stages. "In research risk is shared," she said. "In the first stage, few people are exposed to the drugs so that if it has a problem, not many people will be affected. We also look at its safety and if people can accept the drugs.

The second stage has more people involved spread across the board in different environments and if safety issues look promising, the trial is taken to the third level. The third level is basically one before the substance is put on the market. This particular microbicides trial was in the third stage."