Happy anniversary, protease. So to speak. As year-plus after the advent of protease inhibitors, many triple-drug takers are still in the honeymoon stage, while others are wondering if this marriage can be saved. The headlines out of ICAAC, the Interscience Conference on Antimicrobial Agents and Chemotherapy, in Toronto, Canada, last October: "AIDS Drugs Failing." The media focused on a study by Dr. Stephen Deeks, of University of California/San Francisco, showing that virus had returned in 53 percent of his subjects who had initially gone "undetectable." What this means remains to be seen, since Deeks, the first to publicly deliver such depressing data, said, "All of our ‘failures' are clinically feeling very well. It's important to understand we have no idea of the prognosis of people who have resistant virus." POZ spotted some familiar faces in the crowd of 10,000 and asked for their take on the ICAAC highs and lows.
Dr. Stephen Deeks,
San Francisco General Hospital
"People with HIV should not depend on the mainstream press for accurate information – the data we presented was sensationalized and taken entirely out of context. It suggested that about half of our patients on protease inhibitors had evidence of drug failure. But you have to put these results in the proper context: We looked at the use of these drugs back in 1996, and the patients we followed generally had very advanced HIV and were heavily pre-treated with other antiretrovirals. When we looked only at our patients who were moderately healthy and changed at least one of their other drugs when initiating protease inhibitors, the success rate was closer to 90 percent."
Critical Path Project
"There was good news and bad news – but it will all help us refine how to use this new class of drugs that are more effective than we ever imagined three years ago. Sure, we don't have all the answers on when to start and stop therapy, or on cross-resistance or drug interactions. We often blame patients for nonadherence in situations where there may be drug resistance. But Combivir, the AZT/3TC combination, was approved – and we'll continue to see dosing improvements."
Dr. Paul Bellman,
St. Vincent's Hospital, New York City
"It was a very positive conference. Contrary to the media reports, we learned that it's not inevitable that up to half of all patients will fail on protease-inhibitor therapy. The results of the AZT/3TC/Crixivan trial showed that the benefits lasted for 18 months and counting – and there was no evidence that patients were breaking through and developing resistance. Viracept in combination had similar results. Plus, new information was presented on several new anti-HIV drugs like Sustiva, a very important NNRTI that, when taken with Crixivan, produced extraordinary viral load reductions in almost every patient treated over a 24-week period."
GMHC's Treatment Issues
"It is necessary to have undetectable viral load to become clinically stable? Is going below 400 enough, or do you have to get as close as possible to zero? These are hotly debated questions. Many doctors are still prescribing two-drug combos to people on therapies with low viral loads or are keeping people on therapies that only bring viral loads down to several thousand on the theory that that is good enough for the next several years – until we have more potent drugs and salvage therapies for patients who develop drug-resistant HIV. Others want to beat the virus down to zero. But Dr. Robert Silicano's keynote address here indicated that even after three years of successful highly active antiretroviral therapy, there are still latently infected cells that can produce new virions."
Dr. Cal Cohen,
CRI New England
"The tone was realistic and sober – it wasn't the celebratory Vancouver ‘Wow, we finally figured out the rules of the game.' We're learning the rules and learning just how unforgiving the rules are, too. It was very important because we faced not only our successes, but also what we will do about our lack of success. In terms of protease cross-resistance, the guidelines had been "Switch everything" – until this meeting, where we saw just how that works. You don't see as much success as you want. When these regiments work, they work really well. But there aren't enough safety nets with current meds, so it's a tightrope. Therefore, ‘hit early, hit hard' has to be toned down just a little. It was a best-of-times, worst-of-times meeting."
"I was stressed that here was nothing about vaginal microbicides at a microbiology conference. There was a lot of hype about vaccines, though. It's being constantly reinforced that people with HIV need an HIV specialist to work out all of the details of their treatment with."
Treatment Action Group
"The conference was a big snooze. The failures we're seeing are in heavily pre-treated patients, who we already knew were having problems. When we look at patients with less pre-treatment, we see much better results. What we're hearing from the media is that people are suddenly discovering that AIDS is not over, which anyone watching anti-HIV therapy closely already knew."
ACT UP/New York
"There was a lot to get out of ICAAC, especially in terms of understanding resistance. Most of the data pointed to trying to choose the best possible first-line combination cocktail. It also suggested that after you become resistant, your second-line defenses may not be as successful as we had hoped. The great need for new types of non-cross-resistant protease inhibitors and nukes was overwhelmingly evident."
GHMC's Treatment Issues
"The information about how protease inhibitors are working in people who have been heavily pre-treated was very important. Think of how many were given AZT monotherapy – it is in this group that protease inhibitors are least successful. These patients need individual attention and a regimen tailored just for them. Although progress has been made and there are eleven FDA-approved antivirals, we're still trying to learn how to combine them."