Additionally, in a first-of-its-kind joint announcement, two of the world's leading pharmaceutical companies, Merck & Co. and Bristol-Myers Squibb (BMS) today announced that they have signed separate license agreements with the International Partnership for Microbicides to develop two of the compounds evaluated in the study as potential vaginal microbicides to protect women from HIV. Under the agreements, Merck and BMS each will grant the non-profit group a royalty-free license to develop, manufacture and distribute their compounds for use as microbicides in resource-poor countries. Announced on the eve of the TIME Global Health Summit, this agreement marks the first time any pharmaceutical company has licensed an anti-HIV compound for development as a microbicide when the class of drugs is so early in development.
Women make up nearly half of all people living with HIV worldwide, and 80 percent of new cases of HIV infection in women result from heterosexual intercourse. A vaginal gel containing microbicides could be applied topically to reduce the transmission of HIV and other sexually transmitted infections.
Ronald Veazey, chair of the Division of Comparative Pathology at the Tulane National Primate Research Center, lead author of the paper, conducted the research with simian-human immunodeficiency virus (SHIV), a hybrid virus made in the laboratory from HIV and its cousin, SIV, which infects only monkeys.
The Tulane team tested gels containing two small molecules and a peptide -- alone and in combination --designed to block SHIV from fusing with its target cells at or near the tissue lining of the vagina, to see whether this would prevent the virus from entering the monkeys' bodies. The test compounds were provided by Bristol-Myers Squibb Inc., Merck Research Laboratories and Weill Medical College of Cornell University.
To test the microbicides, the Tulane team first gave the monkeys a long-acting hormonal form of birth control (Depo-Provera) to synchronize their menstrual cycles and thin the vaginal membrane, which increases susceptibility to virus infection, Veazey says. During testing, researchers placed the experimental gels in the animals' vaginas. Thirty minutes later, the animals were exposed to high-dose SHIV.
The three inhibitors were each effective when used alone and also when tested in combination. Of 20 monkeys given the BMS and Merck microbicides in combination, 16 were protected from infection. All three monkeys given the triple combination of microbicides remained virus-free. None of the monkeys experienced vaginal irritation or inflammation from the experimental gels.
"We felt these inhibitors were likely to be pretty safe. Compounds similar to them have a good safety record in humans, at least so far," Veazey says.
"This study demonstrates that combination microbicides are feasible," says NIAID Director Anthony Fauci. "We need to build on these promising animal studies and move toward establishing the safety and effectiveness of combination microbicides in women."