Two Phase III trials of Ushercell (a cellulose sulfate-based barrier vaginal gel being tested for HIV prevention in women during sex) were being conducted in South Africa, Benin, Uganda and India.

This is the second failure of a potential microbicide in a full-scale trial in recent years. In 2000, a large full-scale trial showed that the only other microbicide candidate, nonoxynol-9, was unsafe when it had been expected to be effective.

Women in that trial developed a higher incidence of HIV infection, presumably through ulcers caused by chemical irritation.

In the latest failure the findings of increased risk were identified at some sites in a trial sponsored by CONRAD, a cooperating agency of USAID administered through the Department of Obstetrics and Gynecology at Eastern Virginia Medical School in the United States.

The South African leg of the trial was being conducted in South Africa by the Medical Research Council’€™s (MRC) HIV Prevention Research Unit in Durban.

‘€œAt this point it is not clear why the use of cellulose sulphate was associated with an increased risk of HIV infection in the trial. The Independent Data Monitoring Committee (IDMC), an independent advisory group of experts overseeing the trial, will conduct a detailed review of the data to better understand the findings, and help determine any implications for other microbicide studies,’€ the MRC said in a statement.

  It added that the findings were unexpected as 11 earlier safety and contraceptive trials of cellulose sulfate involving more than 500 participants in Africa, India and the USA, identified no safety concerns.

Recruitment for the CONRAD Phase III study began in July 2005.  The study was conducted in areas of the world where HIV risk is greatest, and where infection occurs primarily through heterosexual intercourse.  

The MRC explained that half of the participating women were given cellulose sulfate, and half a placebo gel, in a double-blinded randomized trial design.    

All participants received intensive HIV prevention counselling at each monthly visit and all women were given high-quality condoms free of charge.  Participants received regular testing and treatment for sexually transmitted infections.  Pregnant women were not included in the study.    

The International AIDS Society (IAS), the world’s leading independent association of HIV professionals, said that while it was important to emphasise the urgent need for the timely development of an effective microbicide to protect women from HIV infection, it also recognized the utmost importance of safety, and applauded the decision to halt the studies to evaluate the preliminary findings.    

  This week, AIDS researchers at the World Health Organization, the United Nations AIDS program and other organizations expressed hope that at least one of three other potential microbicides undergoing full-scale testing would prove to be safe and effective. The others are Pro 2000 by Indevus Pharmaceuticals, BufferGel by ReProtect and Carraguard, whose trademark is held by the Population Council.