I was am reading a lot about the new viral tropism assay from Monogram that may be required as a part of the potential upcoming R5 antagonist labeling. Is this company the only company offering this assay? How does this affect treatment? What are your thoughts on how useful this assay will be?

Thank you for this post. The issue of tropism testing is likely to get increasing attention in the coming months as CCR5 inhibitors move forward in clinical development.

By way of background for other readers, what we are referring to is co-receptor tropism. What was learned some time ago is that HIV-1 usually uses one of two co-receptors to enter the cell, either CCR5 or CXCR4. For reasons that are not completely clear most transmitted strains of HIV-1 appear to use CCR5. These viruses had previously been referred to as nonsyncytium inducing (NSI) viruses and are now called R5 viruses. During the course of infection approximately half of people will have viruses emerge in their blood that use CXCR4. These were previously referred to as syncytium inducing (SI) viruses and are now known at X4 viruses. Although there remains many unknowns, it appears that the emergence of X4 virus is associated with more rapid disease progression.

When the co-receptors were first identified studies were initiated to look for drugs that would block them. There are currently two drugs in clinical development that block CCR5, maraviroc which is anticipated to be available in the United States by expanded access for treatment experienced patients in the coming months and vicriviroc which is a bit further behind in clinical development but also shows great promise. What we know about these drugs is that they block R5 but not X4 virus. Thus far the most promising data has been in those who have been shown to not have detectable X4 virus in their blood using the monogram tropism assay. One study that treated patients that had both R5 and X4 virus in their blood with a CCR5 inhibitor did not show clear evidence of viral suppression, although this was a small study. In any event, based upon the currently available information, in all likelihood these drugs will initially be primarily utilized in those without detectable X4 virus by a tropism assay.

While there are several assays available to assess viral tropism, the Monogram assay is probably the best known and is able to report results relatively quickly. It is also the assay that has been used in the development of the current CCR5 inhibitors. While it is certainly possible that other assays will come on the scene, for now the Monogram test will probably be the one used in the foreseeable future.

Best, Eric