While male condoms prevent HIV transmission fairly effectively, they are not always an option for women in some regions. A method to protect against HIV that women are empowered to use themselves would go a long way in these parts of the world. Recently, researchers have focused on testing vaginal microbicides as such a method, however, none of the microbicides tested so far in large clinical trials have shown a clear effect in reducing HIV acquisition. Now, a group led by VIDI co-director Dr. Julie McElrath and VIDI affiliate investigator Dr. Florian Hladik have devised a method to test microbicides in the lab, to screen candidate medications and shunt only the most effective to clinical trials.
The drugs must eventually be tested in Phase II and III clinical trials before they can go to market, but these and animal trials are expensive and time consuming, so a lab method to test the drugs’ effectiveness in blocking HIV from entering vaginal cells would help hasten the process to finding a working microbicide. In the new technique, the researchers take vaginal tissue samples that are by-products from women who were having vaginal repair surgery, and separate the top skin layers. The scientists then infected these skin cells with HIV, in the presence or absence of five different vaginal microbicides. They tested how effectively the drugs prevented HIV from entering the cells using PCR to look for HIV DNA that had integrated into the genome of the human vaginal cells.
The researchers found that the five microbicides all prevented HIV from entering vaginal cells better than when no drug was applied, with the lipid-soluble version of one of the microbicides, a viral fusion inhibitor called T-20, being most effective. This new model may prove a useful screening step when deciding which drugs to choose for clinical trials.
Ex vivo comparison of microbicide efficacy for preventing HIV-1 genomic integration in intraepithelial vaginal cells. McElrath MJ, Ballweber L, Terker A, Kreger A, Sakchalathorn P, Robinson B, Fialkow M, Lentz G, Hladik F. Antimicrob Agents Chemother. 2009 Nov 30