New AIDS drugs
aim to combat resistant HIV strains

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.

Data from clinical trials of several promising new products will be unveiled at a conference of leading HIV researchers in Los Angeles next week.

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

These include next-generation versions of longstanding HIV fighters as well as drugs that combat the virus through innovative mechanisms, including blocking it from entering immune-system cells.

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.

About half of U.S. patients treated for infections with HIV have stopped responding to at least one drug, said John Mellors, chief of infectious diseases at the University of Pittsburgh.

Resistance is becoming a problem because the virus can mutate, particularly if patients fail to rigorously follow complicated drug regimens.

On Tuesday, Merck 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.

"It looks like a very exciting result," said Mellors. He said clinicians are starting to see response rates in patients previously heavily treated for HIV that are similar to effectiveness seen among first-time patients.

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

Norbert Bischofberger, head of research for Gilead, said comparisons with Merck's data would be problematic because patients in the Gilead study were not allowed to use other therapies until the company obtained information on potential drug interactions.

About four months into the six-month Gilead study, patients were allowed to use protease inhibitors, a commonly used family of HIV drugs, he said.

Another promising 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 Tuesday, Pfizer 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.

Because CCR5 inhibitors do not attack the virus itself, as all four existing classes of HIV treatments do, Mayer said HIV might be less able to come up with ways of resisting their effects.

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

The 14th Conference on Retroviruses and Opportunistic Infections will be held at the Los Angeles Convention Center. (Deena Beasley and Ransdell Pierson, Reuters)