 |
|
|
| |
Maraviroc (MVC) Intensification for Suboptimal CD4+ Response Despite Sustained Virologic Suppression: ACTG 5256
|
| |
| |
Reported by Jules Levin
17th CROI Feb 16-19 2010 SF
TJ Wilkin1, C Lalama2, A Tenorio3, A Landay3, H Ribaudo2, J McKinnon4, R Gandhi5, J Mellors4, J Currier, R Gulick1
1Weill-Cornell Medical Coll., New York, NY; 2Harvard Sch of Public Health, Boston, MA, 3Rush University Medical Ctr, Chicago, IL;
4Univ. Of Pittsburgh School of Medicine; Pittsburgh, PA; 5Massachusetts General Hospital, Boston, MA; 6Univ. Of California; Los Angeles, CA
ABSTRACT
Background: Despite viral suppression, antiretroviral therapy (ART) does not restore CD4 counts in some patients. MVC use is associated with enhanced CD4 recovery in patients who initiate ART. We therefore studied the effect of ART intensification with MVC on CD4 counts in patients with suboptimal CD4 recovery.
Methods: Single-arm pilot trial in subjects with a CD4 count <250/µL, a calculated CD4 slope between -20 and + 20 cells/µL/year and undetectable plasma HIV-1 RNA for the 48 weeks prior to entry. Subjects added MVC, a CCR5 antagonist, to their existing ART regimen for 24 weeks. The primary endpoint was the change in CD4 counts from the average of the 2 baseline counts to the average of the week 22 and 24 counts on MVC. Extensive immunophenotyping was also performed at baseline, week 22 and 24. With a planned sample size of 32, MVC intensification would be considered successful if a CD4 count increase of <20 cells/µL was excluded based on a one-sided Wilcoxon signed-rank test.
Results: 34 subjects were enrolled. The median age was 50; 10 (29%) were non-white; 2 (6%) were women; the median baseline CD4 count was 153/µL. The median duration of HIV-1 RNA suppression was 3 years prior to entry. Two subjects discontinued MVC for virologic failure and were excluded per protocol. A CD4 count increase of <20 cells/µL was not excluded for the primary endpoint (p=0.97). The median increase in CD4 count to week 22/24 was 12 cells/µL [90% CI 1, 22]. Only 2 subjects had a CD4 increase of ≥50 cells/µL. The median baseline immune activation and apoptosis markers in the CD4+ and CD8+ subsets and the change to week 22/24 are shown below. The change in %CD38+ was not associated with CD4 gain.
Conclusions: Adding MVC to a suppressive antiretroviral regimen was not associated with the hypothesized increase in CD4 counts. MVC intensification was associated with decreased immune activation as evidenced by reduced %CD38+, % HLA-DR+/CD38+, and improvement in markers of apoptosis. The clinical significance of these findings is unknown. Further studies of CCR5 antagonists to dampen immune activation associated with HIV infection are warranted.
RESULTS
|
| |
|
|
|
|
|
