IAS: Cancers Worry Vicriviroc HIV Researchers

SYDNEY, July 25 -- Malignancies still plague a major study of the investigational HIV drug vicriviroc, which blocks one of the pathways the virus uses to enter target cells, a researcher said here.

Seven cancers of different types have developed inpatients taking the drug in a placebo-controlled, dose-finding study, including two recorded since last summer when earlier data was presented at the World AIDS Conference, reported Roy Gulick, M.D., of Cornell University.

That compares with only two malignancies among patients getting placebo, Dr. Gulick told attendees at the International AIDS Society meeting.

Exactly why the drug appears to be associated with an increased rate of cancers remains "an open question" that researchers are watching carefully, he said later.

"We've thought about this in great detail and we have an independent committee that has also reviewed all the data," Dr. Gulick said, but no firm conclusions have been drawn yet.

Dr. Gulick noted that the 48-week study is relatively small (118 participants) and includes patients with advanced HIV disease. "We well know that malignancies occur in this group," he said, so the finding could simply be a matter of chance.

On the other hand, vicriviroc binds to a receptor - CCR5 - on the surface of CD4-positive immune cells, so it's "biologically plausible" that the drug is causing decreased tumor surveillance, Dr. Gulick said.

But he noted that the other major entry among the new CCR5 inhibitors, maraviroc (Celsentri), has been tested in many more patients and there's been no sign of an increased cancer risk.

The study is now over, Dr. Gulick said, but he and his colleagues will be following participants for the next five years to keep an eye on the malignancy question.

Clinicians will be keeping a close watch on the progress of trials of vicriviroc, said AIDS clinician Jose Ramon Arribas, M.D. of La Paz Hospital in Madrid, who chaired the session.

"I can't say it has been proved that vicriviroc produces malignancies by any means," Dr. Arribas said, "but it's very concerning."

He echoed Dr. Gulick's caution that the cancers have not been seen in trials of maraviroc, but added: "This has to be watched very carefully."

Aside from the malignancies of various types, Dr. Gulick said, the drug was generally well-tolerated, with equivalent numbers of grade three and four adverse events in all arms.

The researchers enrolled 118 participants who were failing an anti-retroviral regimen and randomized them to placebo or five, 10, or 15 milligrams of vicriviroc added daily to their failing regimen for 14 days.

The five-milligram arm was stopped because of lack of efficacy, he said.

The participants had a median 36,380 copies of HIV RNA per milliliter of blood and a median CD4 cell count of 146 per microliter, Dr. Gulick said. Ninety-two of them had HIV that used the CCR5 receptor to enter target cells.

The drug produced a potent and durable reduction in HIV viral load by about a factor of 100, on average, he said.

At week 48, 10% of those on placebo had undetectable HIV -- defined as fewer than 50 copies per milliliter -- compared with 30% and 40% in the 10- and 15-milligram vicriviroc arms, respectively.

At the same time, the average CD4 cell count increased by 100 to 130 cells per microliter of blood.