HIV 'Locked Out' of Human Cells With New Drugs
Jan. 31, 2000 (San Francisco) -- Breakthroughs in understanding how HIV gets into cells are leading to a new class of AIDS drugs -- and maybe to an AIDS vaccine. Studies presented here at a meeting of HIV researchers promise that new and better medicines may soon be added to the current AIDS drug "cocktails."
The first of this new class of agents, called entry inhibitors, that can stop HIV from infecting cells is called T-20 and is already making waves. "We have a potent new therapy," says Samuel Hopkins of Trimeris Inc., based in Durham, N.C.
Hopkins announced new findings in the first group of patients to get T-20: people whose immune systems are failing even though they have tried nearly every HIV drug. As reported at last year's HIV meeting, the addition of T-20 to their drug regimen dramatically lowered the amount of HIV in their blood. Now Hopkins says that these improvements continued for at least 32 weeks and that the number of immune cells in these patients increased greatly. Treatment was well tolerated and the patients took the drug as prescribed -- even though it is given as two injections under the skin each day.
"My personal view is that initially its use will be limited to patients with few other treatment options," says Robert Schooley, MD, of the University of Colorado. "It should launch a feeding frenzy of [companies] hoping to develop [oral drugs that work similarly]."
Despite its drawbacks, the lack of other AIDS therapy options already is creating considerable excitement over T-20. "I don't think there has ever been so much demand in the field," Hopkins says. "But I am confident that manufacturing [enough of the drug] is not going to be an issue."
Entry inhibitors stop the first stage of HIV infection: the complex process by which the virus sticks to the surface of a person's cells and fuses to it. This process involves several stages, and each stage offers a target for therapy. One major type of compound -- which includes T-20 -- takes aim at the virus, while another type takes aim at protecting the human cell from infection.
Early in the process of infection, a key HIV protein -- gp41 -- changes into a "hairpin" that picks the "locks" on the outside of a human cell, revealing a deep pocket. T-20 blocks this pocket, which is vital for HIV to invade the cell.
The same group, led by Peter Kim, PhD, of MIT's Whitehead Institute, also hopes that their discoveries can lead to an AIDS vaccine.
Other researchers seek to protect human cells from HIV infection by testing the same "lock and key" mechanisms. Preliminary studies of these agents are promising. According to Hopkins, the entry inhibitors open up new avenues to fight HIV disease: "The compounds we are talking about today hold tremendous promise."