Drug Protects Monkeys from AIDS in Experiment

A souped-up version of a naturally occurring immune system protein can protect female monkeys from the AIDS virus, scientists reported on Thursday in a finding they say may lead to a new way to prevent infection in people.

They hope to eventually use their discovery to develop a microbicide — a cream or gel that women and men could use to protect themselves from sexual transmission of the deadly virus. With 43 million people infected and more than 25 million already dead from the incurable virus, a microbicide would be a valuable way to help fight the epidemic. “The vast majority of HIV infections in the world are sexually transmitted, most commonly through heterosexual sex,” said Dr. Michael Lederman of Case Western Reserve University in Cleveland, Ohio, who helped lead the international study. “But there has been substantial debate as to how the virus actually gets into cells at these sites of transmission, called mucosal sites.” The human immunodeficiency virus that causes AIDS uses molecular doorways called receptors to get into CD4 T-cells, the immune system cells that HIV infects. One of these receptors is called CCR5. “We knew that people with a mutation whose CD4 cells’ surface lack CCR5 are almost completely protected from acquiring HIV infection,” Lederman said. It was also known that an immune system messenger chemical or chemokine called RANTES can attach to CCR5 and keep HIV from getting in. ‘A PRETTY HEFTY DOSE’ Robin Offord and Olivier Hartley of the University of Geneva in Switzerland developed a special form of RANTES that did this especially well. The team worked to dissolve their new chemical in saline solution and then tested it to see if it would protect monkeys. It did, they report in this week’s issue of the journal Science.They put the solution into the vaginas of female rhesus monkeys and 15 minutes later put in a solution containing SHIV, a hybrid of the human HIV and the simian version of the virus that infects monkeys. The highest dose of PSC-RANTES protected all five monkeys that got it. The second-highest concentration protected four out of five monkeys treated, while a slightly lower concentration protected three of five animals. “It took a pretty hefty dose to get protection in the rhesus monkeys,” Lederman said in an interview. “In reality this is pretty pricey.” But in laboratory tests, the chemical prevented the virus from infecting cells for a full day. That could mean a woman could use a gel or cream 24 hours before having sex and still be protected, in theory at least. The Swiss team is now working on a cheaper and easier way to make the RANTES molecule. Lederman said his team wants to test the compound in people. He said it appeared to be safe and did not cause irritation in the monkeys — something important for a microbicide used in the vagina or anus. AIDS experts agree that women and some men need an alternative to condoms to protect themselves from the AIDS virus. In many instances women are unable to refuse sex from husbands or other men and, even more commonly, men refuse to use condoms. Several groups are working to develop microbicides but advocacy groups complain the field is not funded as well as it could be. (Source: Reuters, Oct 2004)