October 26, 2008
A study presented at the joint 2008 ICAAC/IDSA in Washington, DC found the second generation Trofile test is better at predicting the success of Schering-Plough's experimental CCR5 drug, vicriviroc.
The study was a re-analysis of the ACTC 5211 study, which compared vicriviroc to placebo, each taken with optimized background therapy (OBT) in people with experience taking HIV treatments. The original study used the first generation Trofile test, done by Monogram Biosciences, to assess whether the volunteers' HIV used only CCR5 (R5) to enter cells, or if it could use another co-receptor called CXCR4 (X4).
This enhanced Trofile test -- also from Monogram -- has been shown in other research to be better able to detect smaller amounts of HIV that uses X4. The researchers wanted to see if it would better predict whether a person was likely to experience benefit from taking vicriviroc compared to the first generation test.
Overall, the enhanced test found 25 more cases of X4 HIV, out of 114 samples that had originally tested R5 only. Of those 25, 15 had been randomized to take vicriviroc, with 12 experiencing early treatment failure. This suggests that the new test is indeed more accurate at predicting whether people are likely to benefit from vicriviroc, and probably any other R5 drug, like Selzentry (maraviroc).
An audience member pointed out an important potential weakness of this analysis. The researchers did not assess what, if any, affect the other drugs used in the study had in the proportion of people with undetectable HIV. It could be that most of the added benefit thought to be from the more sensitive test was really from other drugs being used in the OBT.
While this new test is better able to detect small amounts of X4 HIV, some HIV doctors and researchers are not altogether convinced that this is a good thing. One Selzentry study found higher CD4 counts in people with X4 HIV despite no reductions in HIV levels. Most doctors and some insurers are requiring the Trofile test to show R5-only HIV in order for Selzentry to be used. Some fear that this new, more sensitive test will further restrict use of this new class of drugs from people who could theoretically benefit from it.
It is important to emphasize that any benefit from a R5 drug even without reducing HIV levels is theoretical. While it was seen in one study, there are several potential reasons for the finding. It's also important to note the study included a small number of people, and it has not been reproduced by others.
For now, this study only shows that the enhanced Trofile test is better at predicting benefit from vicriviroc, and presumably Selzentry. Use of this more sensitive test in the further development of vicriviroc -- and other R5 drugs -- may lead to better treatment outcomes for study volunteers.