A new class of AIDS drugs that inhibit the HIV virus from entering and infecting cells may be effective in AIDS patients infected with resistant forms of virus that do not respond to commonly used multi-drug combinations of antiretroviral therapy.
Emory University School of Medicine physicians at Atlanta's Ponce de Leon Center -- part of Grady Health System -- are participating in the first of several planned multi-site NIH-sponsored randomized Phase II clinical trials testing the new class of AIDS drugs called "co-receptor binders." The drugs already have been tested for safety in a Phase I trial in a small group of patients.
"More and more people are becoming infected with a resistant form of the HIV virus, or they have a form of the virus that over time has become resistant to commonly prescribed drugs," says Jeffrey Lennox, MD, professor of medicine (infectious diseases) at Emory University School of Medicine and medical director of the Ponce clinic. "If proven to be safe and effective in a larger group of patients this new kind of therapy will give us another weapon to treat patients who are failing to respond to current classes of drugs, including protease inhibitors and reverse transcriptase inhibitors."
The currently available drug classes have been effective because they block the ability of the HIV virus to copy itself inside the immune cells it infects. Co-receptor inhibitors work by helping block the HIV virus from entering the immune cells in the first place. HIV normally enters the cells it infects by first attaching itself to a protein on the cell's surface.
Scientists have discovered that the virus requires a second entryway as well, however. This second necessary receptor, which varies depending on the particular type of cell, is called a co-receptor. "These co-receptors could help explain why some people are naturally resistant to HIV infection," said Dr. Lennox. "If an individual inherits a defective co-receptor, their disease could progress more slowly."
Co-receptor inhibitors are recently discovered chemicals that bind to the co-receptors and thus block HIV from entering and infecting the cells. Co-receptor inhibitors are synthetic versions of chemicals similar to those produced naturally by CD8+ immune cells that are already known to suppress HIV infection.
The first clinical trial at Emory of the co-receptor inhibitors is testing a drug designed to block the CCR5 co-receptor, which is present on a variety of immune cells that can be infected by HIV. The trial is being conducted by the NIH-funded AIDS Clinical Trials Group at 20 sites around the country, including the Ponce Center.