Hello. This is Dr. Paul Sax, from Brigham and Women's Hospital and Harvard Medical School. Today I would like to review another interesting study from the AIDS 2014 Conference in Melbourne, Australia.
It is the MODERN study. The MODERN study was the only major clinical trial in treatment-naive patients that was presented at the conference, and it was a comparison between maraviroc and tenofovir/FTC in treatment-naive patients.
The investigators had to screen about 1600 patients to find the 800 who ultimately participated. The reason for the large number of screened patients and screen failures is that any study of maraviroc has to have documentation that the patients had the R5 virus. The largest proportion of patients who were screen failures either didn't have R5 virus or there was some other problem with the tropism assay.
An additional entry criterion was that the CD4 count had to be > 100 cells/µL. All patients received darunavir/ritonavir, and then they were randomized to receive either tenofovir/FTC as the control arm or maraviroc at a dose of 150 mg once daily.
The results at 48 weeks demonstrated that maraviroc was inferior to tenofovir/FTC. Virologic suppression was 77% (maraviroc) vs 87% (tenofovir/FTC), and the performance was particularly poor in patients with lower CD4 counts or HIV RNA > 100,000 copies/mL. No new safety issues were identified with maraviroc.
This raises the question of why the maraviroc arm did so poorly. One possibility is a dosing issue. The 150 mg once-daily dose is not the US Food and Drug Administration (FDA)-approved dose. However, extensive data were cited by the presenter, supporting that pharmacokinetic exposures to maraviroc should be suitable at this 150-mg dose.
Another possibility is that we are not picking up all of the non-R5 virus when patients are screened, a possibility that is suggested by the fact that the CD4 count was the determinant of outcome. The lower the CD4 count, the worse patients did, and that suggests that maybe the tropism assays that were tested in this study were not sensitive enough.
There is the more difficult virologic question of whether CCR5 antagonists can be as good as comparator drugs in this setting. Data from the MERIT study showed that maraviroc was slightly worse virologically than efavirenz, and vicriviroc studies done before that drug was no longer being developed suggested suboptimal responses.
We are left with the question of when we should use maraviroc. The MODERN study will not change clinical practice today because we weren't using maraviroc much for initial therapy. However, the hope is that this novel drug, which has a unique mechanism of action, will ultimately find a role in HIV therapy, either with some of the cure strategies that are being tried, with some of its immunomodulatory properties, or even for prevention.
That is a review of the MODERN study from the AIDS 2014 Conference in Melbourne.
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Cite this: AIDS 2014: In MODERN Trial, Maraviroc Inferior to Tenofovir/FTC - Medscape - Sep 05, 2014.