IAS: Novel HIV Entry Blocker Found Safe and Powerful

SYDNEY, July 24 -- A novel HIV drug aimed at barring entry of the virus into the cell was safe and had a long half-life in an early trial, lowering viral load for up to two weeks after treatment stopped, a researcher said here.

The drug -- known as INCB009471 -- also had a long-term anti-HIV effect that lasted for up to two weeks after patients took their last dose, according to Calvin Cohen, M.D., of the Community Research Initiative of New England and Harvard Medical School.

One possible benefit of the long period of efficacy is that the drug might be taken every few days, rather than once or more times a day, Dr. Cohen told listeners at the International AIDS Society meeting.

But of more tangible benefit, he said, might be the fact that the drug would be more forgiving for people who missed a dose, unlike most current HIV drugs.

The drug is the newest member of the so-called CCR5 inhibitors, which block one of the molecular pathways HIV uses to enter its target cells, Dr. Cohen explained.

Also in the class are maraviroc (Celsentri) -- expected to be launched soon -- and vicriviroc, which is further from market.

Dr. Cohen reported the first data on the drug, from a small study of 23 HIV patients who were randomly assigned to get either a placebo or 200 milligrams a day of INCB009471 for 14 days and then followed for another two weeks.

No other HIV drugs were used during the study, he said.

Patients in the study had an initial viral load of about 40,000 copies of HIV RNA per milliliter of blood, and an average CD4 cell count of 639 per microliter for those getting placebo and 531 for those getting the drug.

Patients getting the drug had a sharp drop in viral load, a factor of nearly 100 by day 16 of the study -- two days after the drug was stopped. Average viral load then started to rise again, but even by day 28 it remained below baseline by a factor of nearly 10, Dr. Cohen said.

The results were the same whether or not patients had previously been treated for HIV, he said. "The curves are essentially superimposable," Dr. Cohen said.

Various strains of HIV enter cells using the CCR5 receptor, another receptor dubbed CXCR4, or both. One potential effect of blocking CCR5 is that other strains that use either CXCR4 or both can arise, which may accelerate the progression of HIV.

But in this small study, Dr. Cohen said, only two patients had what is called a "tropism switch."

There were no serious adverse events and none of the patients dropped out of the study because of side effects, he said. The drug's developers plan to enter later-stage trials using the 200-milligram dose, he added.

The drug "looks very promising," said AIDS clinician Jose Ramon Arribas, M.D., of La Paz Hospital in Madrid, who chaired the session. But, Dr. Arribas cautioned, the study is very early in the clinical trial process.

Nevertheless, he said, the long period of efficacy could be "very exciting for patients" if the drug passes future tests.

"Of all the drugs we have," he said, "so far it has the longest half-life."