[Treatment Horizons]

by Chael Needle

Seaweed and the prevention of HIV—what’s the connection? Well, seaweed contains carrageenan, the active ingredient in the microbicide candidate Carraguard. Developed by the Population Council, an international, non-profit organization that conducts biomedical, social science, and public health research, Carraguard is a non-contraceptive vaginal gel that has been shown to block HIV infection, as well as herpes simplex virus 2, human papilloma virus, and gonorrhea infection, both in vitro and in lab animals.

Carrageenan’s safety has already been recognized by the FDA; the ingredient has long been used as a food-thickener and as an emulsifier in topical creams and lotions. So perhaps it was no surprise that earlier studies on HIV-negative, sexually abstinent women showed Carraguard (across different carrageenan-based formulations) to be safe for use in the vaginal canal, so far for up to twelve months. Specifically, this means that it does not significantly irritate the reproductive tract or become degraded in the vaginal environment.

“The vagina has a very low pH, which can degrade a lot of products, or the normal vaginal flora can degrade some products and deactivate them. Carraguard is not affected by either one of those [processes],” says Robin A. Maguire, a program manager for microbicides at the Population Council’s Center for Biomedical Research who initiated the product development of Carraguard. “[Carrageenan] comes from seaweed...so it’s learned over the millions of years to protect itself so it doesn’t get broken down by harsh environments. By not being broken down, and not being systemically absorbed, Carraguard remains in the vaginal canal for a long period of time, and we know from animal studies that it remains active for up to eighteen hours.”

Carraguard ostensibly works because carrageenan has a negative charge density, which means it boasts a lot of sulfate groups, distributed along the outside of the molecule, says Maguire. This arrangement “causes [the compound] to bind either to virus particles or cells that are infected with HIV, thereby coating it so the virus itself or the cells containing HIV cannot adhere to cells that line the vaginal canal. If you can’t get adhesion, you can’t get infection.” She adds: “We also know that it is very compatible with the mucous cells in the vaginal environment, and that it can even coat the [mucous] cells themselves. So, if an uncoated virus particle or a cell containing HIV is introduced during intercourse, it can’t go up and adhere to the vaginal cells.”

Carrageenan was first selected out, after a battery of assays, from a class of compounds called sulfated polysaccharides. The Council’s researchers zeroed in on this class of compounds because sulfated polysaccharides were long known to have antiviral properties but had been abandoned because they also thinned blood—an undesirable effect, says Maguire. Their antiviral properties might be effective, however, in a topical microbicide where the product would not be systemically absorbed into the body or bloodstream. The Council found that carrageenan-based compounds were the most promising.

Carraguard is now being studied for efficacy in a Phase III South African clinical trial at three different sites and is one of the first products of its kind to advance so far in the research pipeline. This randomized, double-blind, and placebo-controlled trial has enrolled 6,270 women and will last approximately three years. The participants are non-pregnant, HIV-negative women.

The Council is also looking at second-generation microbicides, including ones that potentially would have greater efficacy toward HIV and protect against a wider range of STIs, ones that could be used after sexual intercourse, and ones that would provide contraception. But the focus continues to be finding a microbicide that is viable. Notes Robin A. Maguire: “If we can get proof of concept in a microbicide—meaning we can find a product that works—it would be great for the field but also for women worldwide to help them protect themselves against HIV.”

Chael Needle wrote about testosterone-therapy to rebuild muscle mass in HIV-positive women in the July issue.

August 2004