New Drugs on the Horizon to Battle HIV

"There is a confluence of new drugs in the pipeline that people are pretty excited about," said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.

More than 25 years into the AIDS epidemic, many drugs are used to treat HIV, but an alarming number of patients are becoming resistant to therapy, driving research into new ways to combat the virus. About half of U.S. patients treated for infections with HIV have stopped responding to at least one drug, said Dr. John Mellors, chief of infectious diseases at the University of Pittsburgh.

Drugmakers Merck, Pfizer Inc. Gilead Sciences and Johnson & Johnson are expected to present new clinical data at the annual Conference on Retroviruses and Opportunistic Infections, Feb. 25-28 2007 in Los Angeles.

On Tuesday, Merck & Co. will release results of a trial of MK-0518, which is likely to be the first in a new class of drugs, known as integrase inhibitors, designed to block genetic information needed for HIV to reproduce. Merck plans to seek U.S. approval for the drug in the second quarter.Also on Tuesday, Pfizer Inc.will present data from a late-stage trial of its CCR5 inhibitor, maraviroc, now awaiting U.S. and European approval. Patients in the trial had fared poorly on previous HIV treatments.

“If maraviroc is approved, it would change the landscape of treatment and be the first new oral class of HIV treatments in a decade, since the approval of protease inhibitors,” said Howard Mayer, a Pfizer executive in charge of maraviroc’s development. This new class of medicines works by blocking HIV from entering and taking up residence in T cells, a type of white blood cell vital to the immune system. The drugs work by jamming receptors — or docking stations — that dot the surface of the T cells and act as doorways into the cells. If HIV is barred entry, the virus cannot replicate. Because the receptors are made of a protein called CCR5, the crop of drugs are called CCR5 inhibitors.

On Wednesday, Gilead Sciences Inc., maker of top-selling HIV pill Truvada, will present data from a mid-stage trial of its experimental integrase inhibitor, GS-9137.

Also on Wednesday, Johnson & Johnson, which last year launched its first AIDS drug, Prezista, will announce results from a mid-stage trial of its next-generation non-nucleoside reverse transcriptase inhibitor, known as TMC278, which works by blocking an enzyme the HIV virus needs to replicate.

HIV (human immunodeficiency virus) to successfully replicate itself, the virus must first infect a host cell and integrate itself into the cell's genome. Three enzymes in the body help the virus accomplish this task: reverse transcriptase, protease and integrase. Once HIV gets cozy inside a host cell, it turns that cell into an HIV factory, capable of churning out new copies of the virus to seek out and infect new cells.

There are currently three major classes of antiretroviral drugs used to treat HIV. Two of these classes work by inhibiting the action of the reverse transcriptase enzyme; the third class inhibits the protease enzyme. Modern HIV therapy, which involves patients taking a cocktail of these drugs, does a remarkable job of tamping down the virus to undetectable levels. HIV and AIDS (acquired immune deficiency syndrome) used to kill patients quickly but now have been somewhat defanged, and HIV infection is treated more like a chronic disease. (There is still no "cure" for HIV because under current therapies, the virus is never 100% eliminated from the body.)

The human immunodeficiency virus that causes AIDS infects more than 1 million people in the United States and nearly 40 million worldwide. An estimated 40,000 Americans become infected each year.