Looking Back to Look Forward

So where are we going in 2006 with HIV treatment? There certainly are new drugs on the horizon, but there is also a current drug whose full potential has not yet been tapped. With stable patients'those whose viral loads have remained below 50'we have spent the past year simplifying regimens to ones that are once-a-day, have fewer pills, or have less long-term toxicity. But for those challenging patients who are resistant to three drug classes, what are the next options in the cat-and-mouse game with HIV? The goal is often to create a salvage regimen that halts or delays CD4-cell decline while we wait for one or (hopefully) two new antiretrovirals that will enable the creation of a new regimen to which the virus is fully susceptible. Until the integrase inhibitors and CCR5 and CXCR4 attachment blockers move to broader access, salvage regimens may need to rely on the use of Fuzeon to enhance viral suppression when added to ritonavir-boosted protease inhibitors. A study released in October at the Infectious Diseases Society of America conference had looked at the benefit of adding Fuzeon in three different salvage regimens for patients with three-class resistance. Patients had an average CD4-cell increase of 86 to 136, a viral load of 40,000 to 125,000, and experience with 11 different antiretrovirals when they entered the studies. The Toro study used boosted Kaletra, the Resist study used boosted Aptivus, and the Power study used boosted TMC-114, the new Virco protease inhibitor. In all three studies the percentage of patients who reached undetectable viral loads at six months (less than 400 in Toro and Resist, less than 50 in Power) went from approximately 30% without Fuzeon to 60% with Fuzeon. The take-home message: Add Fuzeon and you double the success of reaching undetectability. Thoughtfully, the durability of this response will probably depend on the number of baseline protease mutations. So this may mean that delaying the use of Fuzeon in salvage and thus allowing more mutations to develop may be sacrificing the possibility of long-term HIV suppression, especially in patients who have yet to build up a big list of protease inhibitor mutations. None of us have crystal balls, but hesitancy to use Fuzeon may cause the loss of the opportunity to achieve durable suppression. No one can deny that some reluctance to use Fuzeon is the undesirability of twice-daily injections. But two new options help mitigate this problem. New studies show that smaller-diameter needles and the needle-free Biojector improve the tolerability of injections, improving patients' quality of life. When physicians know that patients are more accepting of Fuzeon administration, they are more comfortable offering it. The newer needles are both shorter and thinner in overall diameter, causing less discomfort. But because the wall of the new needle is also thinner, the internal diameter still allows for easy administration of Fuzeon. The Biojector, which uses a gas cartridge to propel Fuzeon through the skin, appears to cause less injection-site reaction. In addition, it enables the patient to access difficult-to-reach areas, such as the outer upper arms, hips, or buttocks. And for those with needlephobia, it is a great solution. Biojector has limited availability through BioScrip, which is participating in the trial to document its acceptance and success. Hopefully, the study will be completed by May, allowing for insurance coverage. The future also looks very interesting for Fuzeon and its synergy with CCR5 blockers. There is data indicating that Fuzeon may push HIV toward CCR5 tropism. And in the presence of CCR5 blockers, HIV may be more sensitive to Fuzeon. Finally, there is also data that the Fuzeon-resistant virus is less fit. So in deep salvage with Fuzeon-experienced patients, it may still be useful. Historically, progress in HIV treatments comes in bursts. We get nucleoside analogs. Then we wait until protease inhibitors appear. After a while nonnukes come along. Now we are waiting for the next new classes. But while we wait, Fuzeon may be very useful in bridging the gap. Bowers is board-certified in family practice and is a senior partner with Pacific Oaks Medical Group, one of the nation's largest practices devoted to HIV care.