PI Perspective #47

December 2008     View PDF     En español

More sensitive test leads to better results for Selzentry

by Paul Dalton

A re-analysis of the MERIT study using the second generation Trofile test was presented at the joint 2008 ICAAC / IDSA meeting in Washington, DC. The poster presentation by Michael Saag MD found that Selzentry (maraviroc) was comparable to Sustiva (efavirenz) when used as part of a person’s first HIV regimen.

The poster, titled MERIT ES, looked at data from the MERIT study that was presented at the International AIDS Society meeting in Sydney in 2007. That study found that Selzentry failed to match up to Sustiva, when either was taken with Combivir (zidovudine/AZT + lamivudine/3TC). Oddly, a planned analysis showed that the difference was due to significantly lower rates of success in people taking Selzentry in the southern hemisphere compared to those in the northern hemisphere.

In an attempt to understand this unusual finding, the investigators took a second look at these results using a second generation, enhanced Trofile test, which determines whether a person’s HIV uses only the CCR5 co-receptor (R5-only) to gain entry into cells, or can use another receptor, CXCR4 (X4). The new test is better able to detect lower levels of X4 HIV and therefore might better predict success when using an R5 drug like Selzentry. Another study presented at this meeting found increased success rates of another R5 drug, vicriviroc, when the new test was used.

In the MERIT ES re-analysis, 15% of people of people who were determined to have R5-only HIV were found to have HIV that could use X4. This included those with either a mixed population or a dual virus that can use either co-receptor. There were similar numbers in people randomized to take Selzentry or Sustiva.

When that 15% of volunteers was removed from the analysis, Selzentry proved to be equal to Sustiva in terms of reducing HIV levels and superior in terms of tolerability. After 48 weeks, 68% of people from both groups had HIV levels below 50 copies. On average, people taking Selzentry gained 174 CD4 cells compared to 144 for those on Sustiva.

Overall, 13% of people taking Selzentry reported any adverse event compared to 43% of people taking Sustiva. The difference was due mostly to more frequent central nervous system reactions and rash among people on Sustiva.

This result is good news for Selzentry. Although not specifically addressing the issue of the different response rates between hemispheres, the overall similar rates when using the new more sensitive Trofile test make that observation most likely the result of higher rates of undetected X4 HIV in the southern hemisphere.

While this result is positive for Selzentry and its maker Pfizer, it’s unclear whether it will lead to significant use of Selzentry as part of first line treatment. For one thing, it still requires the Trofile test, which is expensive and time consuming. It is also a relatively new drug, without the long safety record of drugs like Sustiva and Kaletra that are widely used as part of first line therapy. However, like the results from the STARTMRK study, these results should open up wider use of Selzentry earlier in HIV disease.