IAS: CCR5 Inhibitors Eagerly Awaited for HIV Therapy

SYDNEY, July 27 -- A new class of HIV drugs, the CCR5 inhibitors, is designed to prevent HIV from entering cells and should be helpful in disease management if they gain regulatory approval, said researchers here.

"We anticipate these drugs will become part of the clinical arena," said Eric Daar, M.D., of Harbor-University of California Los Angeles Medical Center, at an industry-sponsored symposium at the International AIDS Society Conference.

He reviewed clinical trials for maraviroc, which is pending FDA approval, and vicriviroc -still under going earlier phases of clinical testing. "Clinical trial data from studies with maraviroc and vicriviroc show that this new class of drugs will make a significant impact on the treatment of patients with multidrug-resistant CCR5-only HIV," he said.

Although the CCR5 inhibitors prevent entry of the virus into its target CD4 cells, the drugs work best against virus that seeks only the CCR5 receptor. For that reason, tropism testing -- to determine whether the virus is indeed CCR5 tropic or CXCR4 tropic -- may be necessary.

"I wouldn't treat patients with maraviroc without getting testing for tropism first," said Daniel Kuritzkes, M.D., of Harvard and director of AIDS research at Brigham and Women's Hospital.

He said the test will be available at the time that maraviroc is approved. "We are told that the assay will have a turn-around time of 16 days," he said.

The researchers noted that interest in the entry inhibitors is heightened by the fact that almost all anti-HIV medication is aimed at disrupting the virus's ability to replicate once it invades cells. With the exception of the injected drug enfuvirtide (Fuzeon), all other approved drugs attack from inside the cell.

"Newer agents with extracellular mechanisms of action can target different stages of the HIV life cycle and have different resistance profiles than existing agents with intercellular mechanisms of action," said David Cooper, M.D., DSc, of the National Center in HIV Epidemiology at the University of New South Wales here.

Dr. Cooper, who chaired the symposium, said that the new CCR5 inhibitors "could be used in treatment-experienced patients and potentially in treatment-nave patients and could allow for class-sparing therapies, replacing or delaying the use of more toxic agents."

Dr. Daar explored concerns about whether use of maraviroc or other pure CCR5 entry inhibitors might increase the virus's use of CXCR4, considered a route to a more aggressive form of HIV.

He noted that in studies that specifically targeted patients with non-CCR5 populations of virus, maraviroc still was able to have a positive impact on CD4-positive cell counts, although its impact on virus was negligible.

"It doesn't appear that these patients were harmed by administration of maraviroc," Dr. Daar said. He also noted that concerns about emergence of malignancies among patients on maraviroc turned out to be similar or less than patients on placebo.

Dr. Daar listed possible conflicts of interest with Abbott Laboratories, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Human Genome Sciences, Merck & Co., Monogram Biosciences, Pfizer, Schering-Plough, Tanox and Tibotec.

Dr. Kuritzkes listed possible conflicts of interest with Abbott Laboratories, AnorMed, Avexa, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Johnson & Johnson, Merck & Co., Pfizer, Roche and Virax.

Dr. Cooper listed possible conflicts of interest with Abbott Laboratories, Avexa, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Merck & Co., Monogram Biosciences, Panacos, Pfizer, Roche, Schering-Plough, Tanox, Tibotec, Trimeris, and VIRxSYS.