Experimental Drug Blocks HIV/SIV Transmission in Monkeys, Study Says; Could Lead to HIV-Blocking Microbicide for Humans

An experimental drug has blocked the transmission of an HIV/SIV hybrid in monkeys and may be used in the development of an HIV-blocking microbicide in humans, according to a study published in the Oct. 15 issue of the journal Science, Reuters reports (Fox, Reuters, 10/14). HIV most commonly enters the body through receptor molecules called CCR5. Previous studies have shown that people who lack CCR5 because of genetic mutations "hardly ever" contract HIV, according to the AP/Las Vegas Sun. The body also contains another molecule called RANTES that is able to block HIV transmission by attaching itself to CCR5 before HIV does. For the study, Dr. Michael Lederman of Case Western Reserve University in Ohio and colleagues created a drug version of RANTES "thousands of times more potent" at blocking CCR5 from HIV than naturally occurring RANTES, the AP/Sun reports. The researchers then gave 30 female rhesus macaque monkeys a hormone that made them more vulnerable to HIV infection and applied the drug -- called PSC-RANTES -- inside their vaginas. The researchers 15 minutes later inserted into the monkey's vaginas high doses of a solution containing SHIV -- a hybrid of HIV and SIV, the simian version of HIV (Neergaard, AP/Las Vegas Sun, 10/14).

Results
Of the five monkeys that received the highest dosage of PSC-RANTES, all were protected from SHIV infection, Reuters reports. Four of the five monkeys that received the second-highest concentration of the drug did not contract SHIV and three of five monkeys did not contract the virus when they received a "slightly lower" concentration of PSC-RANTES (Reuters, 10/14). "There is still a lot of work to be done before we have an affordable, easy to use method of blocking transmission of HIV through the vaginal membranes," Lederman said, adding, "But we have taken an important step. [T]he door is open to the development of a topical agent that could prevent infection with HIV in humans" (BBC News, 10/14).

Microbicide Development
While the experimental drug so far has been tested only in monkeys, Lederman said within approximately one year he hopes to test the drug in humans as a potential microbicide to determine if it stings or inflames vaginal tissue, the San Francisco Chronicle reports (Russell, San Francisco Chronicle, 10/15). Microbicides include a range of products such as gels, films, sponges and other products that could help prevent the sexual transmission of HIV and other sexually transmitted diseases. Although HIV is transmitted primarily through heterosexual intercourse in much of Africa and Asia, no female-controlled HIV prevention method currently is widely available (Kaiser Daily HIV/AIDS Report, 7/14). Because PSC-RANTES provided SHIV protection for 24 hours in the monkeys, if it is developed for use as a microbicide in humans, women would be able to apply it 24 hours before intercourse and still be protected from HIV, according to Reuters (Reuters, 10/14). However, the drug -- manufactured by Gryphon Therapeutics -- currently is made in "small quantities, at great cost," the Chronicle reports. Gryphon has developed methods that may be able to increase production and decrease the price of the drug. "Pennies per dose is what we need," Lederman said (San Francisco Chronicle, 10/15). Although two microbicides currently are undergoing final stage testing in women in Africa, they do not specifically target the way HIV enters the body through heterosexual intercourse, according to the AP/Sun.

Reaction
According to Dr. Zeda Rosenberg of the International Partnership for Microbicides, it is "crucial to develop multiple methods" to prevent sexually transmitted HIV, the AP/Sun reports. "Having a drug that specifically blocks HIV's receptors is a really important piece," she said (AP/Las Vegas Sun, 10/14). Jo Robinson of the Terrence Higgins Trust said, "We urgently need new agents to be moved swiftly up the research process in order to ensure that products which are effective and safe to use in humans are made available as soon as possible. A microbicide could prevents millions of HIV infections over a short period of time if we are able to deliver it to those who need it most" (BBC News, 10/14).

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