[Treatment Horizons]                         

by Chael Needle

Alongside increasing the armamentarium of treatment options, researchers are also studying how to prevent HIV transmission in the first place. Preventative vaccine research receives a lot of coverage and funding, but microbicide research lags behind in both respects. Microbicides are among the most eagerly awaited ways to prevent the sexual transmission of HIV and other STDs, especially because women who have sex with men will not have to rely solely on male condom use to lower the risk of infection. Female condoms have been cited as a possible option (and cervical barriers have been theorized as an option) women can use to reduce the risk of HIV, but, with forty percent of HIV-positive women being infected from sex with men, women need more choices. Though it is not currently thought that microbicides will supplant the efficacy of condoms, they would be an important step in putting women in control of their own health?women would be able to use microbicides without their partners? knowledge and will not have to rely solely on their male partners to use condoms.

Defined as any substance that works to reduce the transmission of HIV and/or other STDs, bacteria, and parasites, microbicides could also conceivably work to prevent transmission of HIV from women?s vaginal secretions to men. Formulated as a gel, cream, suppository, among other products, microbicides are topically applied to the vagina or rectum. About sixty microbicide candidates are currently being studied. None have made it to market. Two recent studies on microbicides have possibly moved us steps closer to making microbicides available to sexually active women everywhere.

The first study, published in the July 25, 2003, edition of AIDS, reported the results of testing a vaginal gel containing TMC-120, an NNRTI candidate, in female mice. The mice received a single vaginal application of the microbicide twenty minutes before being infected with HIV-1 cells. The gel works to inhibit the replication of HIV. Dr. Simonette Di Fabio of the Istituto Superiore di Sanita in Rome, Italy, and her colleagues, reported that the gel provided protection rates between seventy and 100 percent at all TMC-120 concentrations tested. Animals receiving the placebo all became infected. This is the first evidence of the in vivo effectiveness of an NNRTI-containing microbicide against cell-associated HIV. Researchers suggest that human studies are needed to further study this microbicide. It should be noted that TMC-120, an NNRTI being developed by Tibotec-Virco, is still in clinical trials and has not yet been approved for use in the treatment of HIV.

A microbicide candidate that is headed for human trials, later this year, is VivaGel, developed by Australian biotech Starpharma. The U.S. Food and Drug Administration approved Starpharma?s application for Phase 1 human trials. Primate trials using macaque monkeys showed that a single vaginal application of the gel proved 100 percent effective against a humanized version of SIV, as well as animal versions of genital herpes and chlamydia.

VivaGel is synthetically produced using nanobiotechnology, an emerging technology that allows for the production of very small plastics, used to build devices to study?and, in this case, treat?biosystems. Its active ingredient is the polylysine dendrimer SPL7013. Dendrimers are synthetic, star-like, globular macromolecules about the size of proteins which have tree-like branching ends, where drugs can be attached or placed within cavities. They are highly water soluble, and can be synthesized to resist being broken down by the body?s systems. VivaGel is meant to be applied about half an hour before sex. Starpharma is also working on a rectal gel for men who have sex with men.

 The trial, which is expected to begin before the end of the year, will initially involve groups of twelve women, with eight using VivaGel and four using a placebo. During the initial trial, women will apply small amounts of the gel once a day for safety reasons. A second twelve-month trial involving at least 8,000 women is expected to follow. If the safety trials are successful, the gel could be on the market as early as 2007.

Chael Needle wrote about insulin resistance?s possible role in increased waist/hip ratio in the August issue.