March 1, 2007 -- "Incredibly exciting." "Road to hope." "Very exciting." "A very important milestone in HIV treatment history."
That's what major AIDS researchers are saying about Isentress, the first of a new class of HIV drugs. Early results from two major clinical trials of Isentress were reported this week at the largest annual U.S. HIV conference.
Patients in the studies had run out of treatment options. After a decade of treatment, the HIV in their bodies had become resistant to at least one drug in each of the three classes of AIDS therapies. Their immune systems had begun to fail and they had high blood levels of HIV.
But when these patients took Isentress in combination with other powerful AIDS drugs, nearly 80% of patients saw their HIV levels plummet to near-undetectable levels after 16 weeks of treatment. Without Isentress, state-of-the-art treatment helped only 43% of patients to this degree.
Joseph J. Eron Jr., MD, of the University of North Carolina-Chapel Hill, reported the combined findings from the studies at the 14th annual Conference on Retroviruses and Opportunistic infections.
"This is a very important milestone in HIV treatment history," Eron tells WebMD. "These are results we would have been happy with in treatment-naive patients. And these are our most drug-experienced, drug-resistant patients -- the ones for whom it is most difficult to come up with treatment options.
"It really moves us into an era where even our most treatment-experienced patients have the opportunity to get their virus below detectable limits," Eron adds.
New AIDS Drug, New HIV Target
HIV makes three proteins, called enzymes, which it needs to infect human cells. The AIDS virus uses its reverse transcriptase enzyme to translate its RNA genetic code into DNA. Later, after it has made human cells produce new viral proteins, it uses its protease enzyme to snip the proteins into the right size.
Nearly all existing HIV drugs block either reverse transcriptase or protease. But Isentress blocks an enzyme called integrase. HIV needs integrase to integrate its newly translated DNA into the DNA of human cells.
Researchers have worked for years to develop an integrase inhibitor. Until recently, that goal was elusive. Now that work is paying off. Isentress, from Merck, is the first of its kind. But others are on the way.
The Isentress results are based on only 16 weeks of treatment, although early 24-week results look as good. Eron warns that the durability of the treatment remains unproved.
Yet normally cautious AIDS researchers say it's been a very long time since they've seen such promising findings.
One is Amneris Luque, MD, medical director of the AIDS Center at the University of Rochester, New York.
"This is the road to hope for people who have failed all other AIDS medications," Luque tells WebMD. "It is very impressive to see these kinds of numbers in patients who have developed resistance to other medications."
Another is AIDS treatment pioneer Margaret A. Fischl, MD, director of AIDS research at the University of Miami. Fischl attended the reports by Eron and others.
"I think everyone at the conference was very impressed by this integrase inhibitor," Fischl tells WebMD. "No matter how you looked at it, you saw the integrase inhibitor did very well."
Fischl, too, pointed to the difficulty of treating the kind of patients in the Isentress study.
"You are looking at patients who had been on potent antiviral therapy for a decade -- and they failed that," she says. "So yes, I am impressed."
Carlos del Rio, MD, chief of medicine at Grady Memorial Hospital and professor of medicine at Emory University, Atlanta, treated many of the study patients.
"It is an incredible drug, an amazing drug," del Rio tells WebMD. "With this drug we are able to see some pretty remarkable results."
So far, Isentress seems remarkably safe. It did not seem to cause any adverse events not seen in patients who received a placebo. Fewer than 2% of patients in the trial dropped out due to adverse events.
But all the experts who spoke with WebMD warn that only time will tell. Many other HIV drugs have shown their toxic side only after extended use.
Like all other anti-HIV drugs, the AIDS virus can become resistant to Isentress. Eron warns that doctors must be very careful about how they use the drug.
"The key here is that we need to remember to work as hard as we can to combine even this new, very active drug with other very active drugs," he says.
Merck -- a WebMD sponsor -- has already begun an expanded access trial for patients who need Isentress. And del Rio says he's already started testing the drug as a first-line AIDS therapy.
"We are getting good results so far," he says.