The approval of enfuvirtide (ENF, T-20, Fuzeon) in 2003 was an important contribution to the effective treatment of triple-class-experienced patients. However, despite both the abundant medical data supporting enfuvirtide's activity, and the improvement in regimens when enfuvirtide is used, there are a few hurdles to its regular use.

Among these hurdles is that enfuvirtide must be given by twice-daily, subcutaneous self-injection. This study explored whether enfuvirtide would be similarly successful if it were given just once a day, thereby reducing at least one hurdle to its use.

The study design compared the short-term activity of regimens in which either the standard 90-mg dose of enfuvirtide was given twice a day or a single 180-mg dose of enfuvirtide was given just once a day.

Thirty-seven people who were in need of starting an enfuvirtide-containing regimen were enrolled and randomized to either once- or twice-daily enfuvirtide.

The mean CD4+ cell count at entry was about 72, and the mean viral load was about 5 log. The design used a crossover approach, meaning that group A took enfuvirtide once a day for 1 week, then switched to twice a day; group B did twice a day first and then switched to once a day.

In terms of drug levels, the total daily "exposure" to enfuvirtide was nearly identical in the 2 arms. In contrast, the trough (lowest level of the day) concentrations did differ somewhat, the once-daily dose had a 57% lower trough compared to the twice-daily dose.

In terms of clinical efficacy, the group which started on twice-daily enfuvirtide (and then changed to once-daily) did consistently a bit better than the reverse schedule by about 0.38 log at day 7, and 0.71 log at day 14 (P = .002).

The analysis showed an association with this difference in response and the trough concentrations, but this was only a partial relationship. There were no differences in adverse events in these 2 schedules.

While these results challenge the hope that enfuvirtide can be as successful when dosed just once a day, the question is felt to be important enough -- and the results ambiguous enough -- to warrant additional study. This is especially true given that, while the end of week 1 showed twice-daily enfuvirtide was more potent than once-daily enfuvirtide, the reverse conclusion was seen from the next 7 days. This, coupled with the fact that these conclusions are based on fewer than 20 people per dose arm, has led to a second study in order to be confident that we have the correct conclusion.

The additional convenience provided by the once-daily injection could certainly assist in making enfuvirtide more attractive, and therefore additional data to inform this question will be important to have.