First treatment for drug-resistant HIV.

Doctors have their first Food and Drug Administration-approved tool to treat drug-resistant HIV thanks to a new molecule created by a researcher at Purdue University, West Lafayette, Ind.

"There are many treatments for AIDS on the market, but none are able to combat drug resistance," points out Arun Ghosh, a professor with a dual appointment in the departments of Chemistry and Medicinal Chemistry and Molecular Pharmacology. "This is the first treatment that is effective against the growing number of drug-resistant strains of HIV, the virus that causes AIDS. The problem is widespread."

This year marks the 25th anniversary of the first U.S.-reported cases of AIDS, a disease that claims the lives of more than 15,000 Americans each year, according to the Centers for Disease Control and Prevention, Atlanta. World Health Organization figures estimate that more than 40,000,000 people worldwide are infected with HIV.

Earlier research shows that almost half of patients with the human immunodeficiency virus who initially respond to treatment develop drug-resistant strains and stop getting better within eight to 10 months. An additional 20-40% have drug-resistant strains when they are first diagnosed, suggesting that these strains can be transmitted from one person to the next.

For years, the virus has frustrated drug developers through its ability to "outsmart" therapies. The virus mutates rapidly and, as parts of its structure change, becomes resistant to treatment. Previously, patients with drug-resistant strains were out of options and had greatly reduced life expectancies. However, the FDA recently approved the pill-based therapy of Ghosh's molecule, TMC-114, for medical use. Also known as Darunavir, it is the forerunner in a series of molecules under development by Ghosh.

Molecules are made up of groups of atoms bonded together. These bonded groups form an oddly-shaped structure with sections that branch off and others that form loops. Different sections are responsible for various behaviors of the molecule. Ghosh's designed compound has selected features of naturally occurring molecules that improve its ability to fight HIV. The result is a variation of one of the most common treatments existing today, a protease inhibitor.

Eight protease inhibitors currently are on the market and have greatly improved the quality of life for those suffering from HIV, Ghosh notes. These inhibitors, however, lose their effectiveness over time, often cause severe side effects, and are of little use against drug-resistant HIV strains.

Treatment using the Ghosh molecule has fewer associated side effects because the dose required is significantly less than those for existing protease inhibitors. The molecule also is smaller than those that make up current protease inhibitors and is much more easily absorbed and tolerated by the body.