October 2002  

Population Council Takes a Leading Role in Emerging
AIDS-prevention Arena

Over the past decade, the Population Council’s comprehensive microbicide program has earned the Council distinction as a leader in the field of microbicide development. Its most promising product, Carraguard™, will be among the first microbicide candidates to enter a large-scale effectiveness trial.

Formulated as gels or creams, microbicides, if proven effective, could be used in the vagina or rectum to provide protection from HIV and other sexually transmitted infections (STIs). Microbicides offer a potentially powerful new approach to addressing the global HIV/AIDS pandemic. For this reason, they have become a priority for the Council’s biomedical, public health, and social scientists, and for dozens of other organizations working in HIV prevention.

Globally, the prevalence of HIV among women is growing more rapidly than among men. This trend in the HIV/AIDS epidemic is driven by social, cultural, and economic conditions that limit women’s ability to protect themselves from infection. In developing countries, women can be especially vulnerable because existing strategies for HIV prevention—mutual monogamy among HIV-negative partners, condom use, and treatment of STIs—are not practical for many of them. Because of an urgent need for a means of prevention that women can control, the Council is developing a vaginal microbicide. Carraguard, which is believed to be noncontraceptive, may allow women to become pregnant, a desirable feature for women who wish to protect themselves from HIV infection but not necessarily to avoid pregnancy.

Product development
Since 1986, scientists at the Council have been exploring how HIV is sexually transmitted. After discovering that HIV infected cells from semen could infect cells lining the vagina and cervix, scientists conducted laboratory studies to test the efficacy of substances to prevent infection. Compounds called sulfated polysaccharides proved especially promising. Among the sulfated polysaccharides tested, carrageenan was the most successful in preventing infection by similar viruses in mice.

Derived from seaweed, carrageenan has long been recognized as nontoxic and stable, even when exposed to extreme temperatures. Inexpensive and abundant, it has been used for decades as a thickener in foods and as an emulsifier in creams and lotions. Although the U.S. Food and Drug Administration had already approved carrageenan as a food additive, Council staff are conducting in-depth preclinical and clinical evaluations necessary to secure its approval as a new active pharmaceutical ingredient. The formulation, Carraguard, appears to be safe and nonirritating, and laboratory studies have indicated its effectiveness against HIV and the herpes simplex virus.

Clinical testing
In the growing microbicide field, nearly 60 microbicide candidates are now in various stages of development by other organizations, with several products undergoing clinical trials. Carraguard is in the forefront, having completed early trials that tested safety and acceptability. Starting in 1996, trials of carrageenan-based microbicides for vaginal use were carried out among healthy, HIV-negative women in six countries, including the United States. Overall, the women reported that the gel was easy to use and did not cause significant irritation.

The Council then conducted safety and acceptability trials in South Africa and Thailand among 565 healthy, HIV-negative, nonpregnant women. The trials were implemented by the University of Cape Town, the Medical University of Southern Africa, and the Thailand Ministry of Public Health–U.S. Centers for Disease Control and Prevention Collaboration. Women were instructed to apply the gel at least three times a week and before each act of vaginal sexual intercourse. Women in the trial received safer-sex counseling and monthly gynecological exams, with testing and treatment of curable STIs. All trial participants were given condoms and encouraged to use them.

A larger-scale trial is now planned to determine Carraguard’s effectiveness in averting HIV infection and other STIs. The trial must be conducted in locations with at least three percent annual HIV incidence to determine whether the product prevents infection. The trial will be carried out with 6,000 HIV-negative women at four sites in Botswana and South Africa. All women will be followed for two years. The trial is projected to begin in 2003, with results expected in 2007.

Working with the community and women's health advocates
While biomedical scientists have worked to develop effective and safe microbicides, public health and social scientists at the Council have worked closely with women’s health advocates and activists to ensure that the ethical and practical challenges of testing and introducing microbicides are taken into consideration. The Council has organized meetings in Thailand and South Africa with public health officials, advocates, and researchers to discuss the trials. In Thailand, the Chiang Rai Community Advisory Group met regularly throughout the safety and acceptability trial to help ensure that the research responded to the needs of the local community. The group will serve as a model for community advisory groups for the effectiveness trial in southern Africa.

Looking ahead
As the Carraguard trials progress, Population Council scientists continue to conduct basic research on HIV transmission and to work on developing second-generation microbicides that may be more effective against a broader range of sexually transmitted infections and have contraceptive properties. Council researchers are also conducting safety trials of Carraguard in HIV-positive women and men and are planning safety studies on rectal use of the candidate microbicide.

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