A pilot trial of adding maraviroc to suppressive antiretroviral therapy for suboptimal CD4⁺ T-cell recovery despite sustained virologic suppression: ACTG A5256

Abstract

Background: Despite viral suppression, antiretroviral therapy (ART) does not restore CD4(+) T-cell counts in many patients infected with human immunodeficiency virus type 1 (HIV-1).

Methods: In a single-arm pilot trial involving ART recipients with suppressed plasma levels of HIV-1 RNA for at least 48 weeks and stable suboptimal CD4(+) T-cell recovery, subjects added maraviroc, a CCR5 antagonist, to their existing ART for 24 weeks. After stopping maraviroc, they were followed for an additional 24 weeks. A Wilcoxon signed-rank test was used to evaluate whether maraviroc was associated with an increase of at least 20 cells/µL in the CD4(+) T-cell count.

Results: A total of 34 subjects were enrolled. The median age was 50 years, and the median baseline CD4(+) T-cell count was 153 cells/µL. The median increase in CD4(+) T-cell count from baseline to week 22/24 was 12 cells/µL (90% confidence interval, 1-22). A CD4(+) T-cell count increase of at least 20 cells/µL was not detected (P = .97). Markers of immune activation and apoptosis decreased during maraviroc intensification; this decline partially reversed after discontinuing maraviroc.

Conclusions: Adding maraviroc to suppressive ART for 24 weeks was not associated with an increase in CD4(+) T-cell counts of at least 20 cells/µL. Further studies of CCR5 antagonists in the dampening of immune activation associated with HIV infection are warranted. Clinical Trials Registration. NCT 00709111.

Trial registration: ClinicalTrials.gov NCT00709111.

Figure 1.

The median change in CD4⁺(A) and CD8⁺ (B) T-cell counts and associated 90% CI during 24 weeks of maraviroc (MVC) administration (+MVC) and 24 weeks after discontinuing MVC (−MVC).

Figure 2.

Change in CD4⁺ T-cell subset markers of immune activation (percentage of HLA-DR⁺/CD38⁺ cells and CD38⁺ cells), maturation (percentage of CD57⁺ cells), proliferation (percentage of Ki67⁺ cells), and apoptosis (percentage of caspase3⁺ cells and Bcl-2⁻ cells) during (A) and after (B) maraviroc therapy. TEMRA, terminal effectors expressing CD45RA. Whiskers, 90% confidence intervals.

Figure 3.

Change in CD8⁺ T-cell subset markers of immune activation (percentage of HLA-DR⁺/CD38⁺ cells and CD38⁺ cells), maturation (percentage of CD57⁺ cells), proliferation (percentage of Ki67⁺ cells), and apoptosis (percentage of caspase3⁺ cells and Bcl-2⁻ cells) during (A) and after (B) maraviroc therapy. TEMRA, terminal effectors expressing CD45RA. Whiskers, 90% confidence intervals.