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Being Alive
A Reason For Hope: ICC Combination Therapy Trials Get Underway
Patrick James
April 5, 1995
Being Alive 1995 Apr 5: 10

I and my weary immune system are going to go way out on a limb to predict that 1995 will be the year in which those of us with HIV/AIDS will have true reason for hope. Medical science may, for the first time, offer proof that the war against this disease is actually turning in our favor. I realize so well that many are very sick and might not make it. And science has learned that there are literally billions upon billions of those vicious little viral villains lurking with their buzzing chainsaws ready to chop off that limb of hope. Nevertheless, I and many others fully believe that there is finally reason for optimism.

Some of the signs of possible impending victory are already fairly well known: ways like quantitative PCR and branch DNA to measure actual viral load (at least six trials so far have proven a definite link between viral load and clinical outcome); the fact that a combination of two unlikely drugs, 3TC and AZT, work together longer and better than any such combination tested; studies indicating great possibilities for protease inhibitors, especially in combination with other drugs. Perhaps more importantly, a "light at the end of the tunnel of perpetual darkness" outlook is starting to be expressed by more and more researchers, clinicians and even activists.

The big question now is: What will be the effect of protease blockers in combination with the already approved nucleoside analogues like AZT, ddI, ddC, with drugs in late-stage testing like 3TC and non-nucleoside RT (reverse transcriptase) inhibitors such as nevirapine and with other treatments like gene therapy, therapeutic vaccines or other things now being developed like "second generation" nucleoside analogues, the cytokines IL-2 and IL-12, plus others? In an article in the October 1994 Being Alive about my own experiences with antivirals and combinations over the past eight years ("The Multiple Drug Approach to Fighting HIV"), I mentioned a collaboration of 15 drug companies, the Inter-Company Collaboration for AIDS Drug Development (ICC), which was planning a fairly large, unique and fairly quick private three-drug human study. Importantly, the ICC's trials will use viral load tests.

The ICC has now chosen 17 sites for its trials. One site, which my source would not identify, has already begun the study. The trial is now enrolling, with a second trial to start as soon as the first is fully enrolled. Other trials will follow.

Two of the sites are in Los Angeles: Harbor/UCLA in Torrance and Pacific Oaks Medical Group in Sherman Oaks. There is one other California site so far, in San Francisco. The 15 companies, soon to be 14, have turned the studies over to a contract research organization, called Parexel. The Parexel information number is 1.800.925.AIDS, 6 am to 2 pm Pacific time. At Harbor/UCLA, the people to call are study coordinator Sally Kruger at 310.222.3848 or Dr. Gildon Beall, 310.222.2365. At Pacific Oaks, it's Dr. Paul Berry, 818.906.6279. In San Francisco call Dr. William Lang at 415.474.4440.

The first of the two ICC planned trials is only for those with CD4 counts of 200-500 who have not previously taken antivirals. There is a limit of 75 patients per site, randomly put in one of three treatment arms. In the first study, all will receive the nucleoside analogues AZT and ddI as two of the drugs. But one group will also receive nevirapine (a non-FDA approved non-nucleoside reverse transcriptase inhibitor), the second group will receive saquinavir (the unapproved Hoffman LaRoche protease inhibitor) and the third will get only a placebo (sugar pill) as its third drug. But this first trial should fill up rather quickly and, when it is full, other groups of 75 will be enrolled in the second trial in which everyone will receive AZT and ddI. One group will get nevirapine as the third drug and a second group will receive 3TC. As I mentioned, other studies are to follow. The first two trials will last 48 weeks, unless startling results cause one or more arms to be unblinded. Again, call 1.800.925.AIDS for the latest, or have your doctor call.

I consider these unique studies to be great news. Using the viral load tests to quickly assay the results adds to the good news. Wellcome PLC's Research Director Dr. David Barry said in the October Being Alive article that a parallel-track program and more traditional trials are planned later for the combinations which show the most promise, in order to get FDA approval as soon as possible.

Adding to the overall outlook for 1995 is something that cannot be overstated: It has been proven that there is indeed good news for those with low T-cells-the immune system does not slowly "die off" as was thought for so many years. Even for people with under 50 T-cells, these key cells continue to be churned out anew by the billions. It's just that, without the right combination of antivirals, at some point the virus starts replicating by more billions than do the CD4s.

But in the December 1994 Being Alive article, "Do Antivirals Work?", I quoted Dr. David Ho, director of New York's Aaron Diamond AIDS Research Center, as saying, "We are dealing with a viral disease. Even in patients with 50 CD4 cells, there should be a doubling or tripling of CD4 levels, sometimes higher. We have seen cases that go up to 350 to 400 [with multiple drug therapy]. . .You realize that the regenerative capacity [for CD4s] is still pretty good." FDA Commissioner Dr. David Kessler, considered by most to be our friend, presided over the recent meeting of the National Task Force on AIDS Drug Development and officially endorsed accelerated approval of protease inhibitors. Dr. Michael Saag of Alabama University, who also attended the meeting, said later in an interview with the San Francisco AIDS publication BETA, "Viral load tests may be one of the most important discoveries since the epidemic began." He said in the same March issue of BETA, "The body's ability to repair itself and produce new cells continues even in the late stages of the disease. . . we shouldn't give up on patients. . .Our goal is to try to suppress viral replication with antiviral agents, preferably in combination." Dr. Jay Lalezari of Mount Zion Hospital in San Francisco was also quoted: "There's been a tendency to despair in advanced HIV... if [CD4] numbers are down in the 5-10 cell range. But the data actually show that these individuals are replacing their CD4 cells at an even faster rate than patients in earlier disease. I think it speaks of an enormous reserve... and capacity for the regeneration of the immune system." Going back to the ICC studies, Dr. Paul Blake, director of research at SmithKline Beecham, recently said something that I can't agree with more. He summed up many years of past drug problems and stated what's finally starting to happen with drug company research and trials in 1995, in a few simple words: "The Alliance is a reminder to everyone working in the field that the enemy is the virus, not other researchers."