Gene defect leads to an AIDS drug
In 1996, scientists solved a mystery surrounding certain gay men who were immune to AIDS. This year,
The US and European researchers, writing in several science journals, said a small group of Caucasian gay men carry a gene mutation that provides natural protection against HIV, the virus that causes AIDS. Last week, culminating an 11-year race among three drugmakers, Pfizer released successful studies of a new pill specifically designed to mimic the gene defect.
"We still remember reading those papers and thinking, 'God, we should do something with this,' " says Pino Ciaramella, a scientist at Pfizer's laboratories in the U.K. seacoast town of Sandwich, where the drug was created.
Regulators in Canada, Europe, and the United States have accelerated reviews of the drug, called maraviroc, based on clinical trials showing that, when combined with other medicines, the pill is more effective than existing therapies in treating AIDS patients. The new drug may gain regulatory approval this year and generate more than $300 million in sales by 2011 for New York-based Pfizer, the world's largest drugmaker. It also may provide a new weapon against forms of the virus that are resistant to current treatments.
Ciaramella says he and his colleagues were spurred into action because the reports involving gay men were followed three months later by a study reinforcing the notion that some people can inherit immunity to HIV. In that research, Canadian and Kenyan investigators reported that 60 prostitutes in Nairobi didn't become infected after being repeatedly exposed to the virus over 10 years.
As a result of the studies, scientists realized that HIV carries out its damage by first hooking onto a spike called a receptor that juts out from the surface of white blood cells, much as a key enters a lock. The gay men of European descent, the scientists found, were shielded from HIV infections by inheriting a defective version of the cell receptor, called CCR5.
Pfizer scientists say this critical finding led them to believe they might be able to create a drug against the virus that worked by binding to the CCR5 receptor, thereby blocking the doorway HIV uses to infect cells.
"The whole thing was started by noticing this genetic defect," says Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland.
Other drug companies, including
Schering-Plough's candidate suffered a setback in 2006 after five patients in one study developed cancer. The company expects to begin a larger trial of the drug later this year after an independent monitoring board ruled there wasn't enough evidence to determine the drug caused the cancers, says spokesman Robert Consalvo.
Maraviroc, when used in combination with other drugs, more effectively suppressed blood levels of the virus than the standard three-drug HIV therapy in current use, according to data Pfizer presented at an AIDS research meeting in Los Angeles on Feb. 27.
Maraviroc may be especially valuable in treating patients for whom existing drugs don't work anymore. Doctors estimate as many as 65,000 people with HIV in the United States are resistant to all three major classes of medications and in worsening health.
Blocking the receptor may lead to unintended effects, including the possibility that the virus may find a way into cells through another receptor, Fauci said.
With reporting by Lisa Rapaport in New York and John Lauerman in Boston. 
