What We Know About Fuzeon

Source : http://www.thebody.com/fuzeon/efficacy.html

Fuzeon -- A Review of the First Entry Inhibitor

By Calvin Cohen, M.D., M.S.
2003

Efficacy: Just How Good Is This Drug?
In initial studies of Fuzeon, it was given to people alone (not as part of a regimen with other drugs) for about one month. This is the standard way to evaluate how powerful an impact a new drug will have on the ability of HIV to reproduce itself. From these studies, we learned that Fuzeon is about as powerful as most of the other potent HIV medications. We saw that an average person's viral load would decline by about 1.5 logs, or about 96 percent, when Fuzeon was used alone as a single drug.

Translating this into viral load: If someone had a viral load of 10,000, a decline of 96 percent would result in a viral load of just under 400. However, since we know that HIV can develop resistance to Fuzeon -- just like HIV does with any other drug when more complete suppression of HIV is not established -- the largest clinical studies on Fuzeon were all conducted with a combination of medications that included Fuzeon, in order to give everyone the best chance possible of suppressing HIV.

Clinical Trial Results
The big clinical studies conducted with Fuzeon were called the "TORO" studies. They enrolled about 1,000 people on several continents. To be eligible, people had to be "treatment experienced" -- that is, they had to have taken all three of the other classes of HIV medications: NRTIs, NNRTIs and PIs. The researchers made this group the target population primarily because they are most in need of a new class of HIV medications -- they are resistant to all three classes of HIV medications and had run out of options for finding a regimen that would durably suppress HIV replication, so they had the most to gain if Fuzeon worked.

The studies were designed to closely resemble what doctors would normally do in their clinical practice, in order to make these trials as easy and as relevant as possible. Patients who were eligible were randomly chosen to receive either the best HIV treatment combination their physician could put together using three to five HIV medications (called the "optimized background"), or this same "optimized background" regimen with Fuzeon added.

To create the optimized background regimen, doctors were allowed to use a combination of three to five of the approved HIV medications that were available at the time. People were given a resistance test before they were accepted into the study so doctors could select the best drugs for them. In addition, doctors had a complete treatment history for each person to help them more accurately choose drugs that would be as well tolerated as possible.

The treatment-experienced patients enrolling in this study had, on average, low CD4 counts and high viral loads. The average CD4 count in these studies was about 90 cells/mm3, and the average viral load was just over 100,000 copies/mL. Nobody took a placebo -- everyone in the study received either the standard "optimized background" regimen, or an optimized background regimen plus Fuzeon.

There was a humane aspect to the design of these studies. If in the first year a person's regimen failed to suppress HIV while on the background arm, he or she was permitted to "cross over" and receive Fuzeon plus a new background regimen.

The results -- which were measured after 24 weeks and again after 48 weeks -- demonstrated the importance of adding Fuzeon to a background regimen. Overall, by week 24, those receiving Fuzeon plus an optimized background regimen had approximately doubled their chances of achieving viral suppression (to either below 400 copies or even down to below 50 copies). This additional rate of suppression occurred since, on average, Fuzeon made the optimized background regimen almost 90 percent more effective. This means that these people had a nearly 90 percent lower viral load than people who were only taking an optimized background regimen.

Of note, those on just the optimized background had, on average, a total viral load drop of only 0.7 log, which is about the same viral load drop that we see when starting a treatment-naive patient on just AZT (zidovudine, Retrovir) alone. This study documented just how much resistance there was among treatment-experienced people in this study.

In summary, analyses of this study demonstrated the success of Fuzeon in people who are already resistant to many other HIV medications. For example, when researchers used one definition of success -- i.e., a viral load that is at least 90 percent lower than at the start of the study -- about twice as many people were able to achieve treatment success after 24 weeks just by adding Fuzeon to their regimen. After 48 weeks, 37 percent of the people taking Fuzeon still had viral load reductions of at least 90 percent, while only 17 percent of people in the optimized background arm were able to maintain such a decline in their viral load.

There are two types of viral load tests: one that can't detect viral loads below 400, and a more stringent one (which is usually used in the U.S.) that can't detect viral loads below 50. Regardless of which measure was used in this study, over twice as many people taking Fuzeon with their regimen had "undetectable" viral loads as people who were not taking Fuzeon. At week 48, for instance, 30 percent of people on Fuzeon had viral loads less than 400 copies, compared to only 12 percent of people on an optimized background regimen alone.
Using the more stringent goal -- reaching a viral load of less than 50 -- 18 percent of people on the optimized background plus Fuzeon, versus 8 percent on only the optimized background, had an "undetectable" viral load to this degree.

Of note, a similar percentage of people with a viral load of less than 400 and less than 50 copies was noted at weeks 24 and 48. This reinforces the idea that lowering viral load to these levels is one important way to achieve a durable degree of viral suppression. As a result of this improvement in people whose viral load was suppressed, there was a corresponding larger increase in CD4 counts when the study reached week 48 in those receiving Fuzeon plus an optimized background (91 cells/mm3 increase) versus those people only on an optimized background (45 cells/mm3).

Resistance Still a Danger With Fuzeon
As with every HIV medication, resistance to Fuzeon can develop. Early studies in which only Fuzeon was used to fight HIV clearly established this. This resistance is made apparent in the form of "genotype mutations," although there are few if any commercial tests that can do such testing now.

What remains less clear so far is how powerful Fuzeon might be even after resistance develops. Is it like other HIV medications, such as 3TC, where HIV can still be partially suppressed even if there is resistance? While research is ongoing to understand this more fully, the research so far suggests that it's possible. Regardless, with Fuzeon (as with any other HIV medication), it is important to attempt to establish robust suppression -- preferably pushing a viral load to less than 50 copies, or at least less than 400 copies.