H-1031

290

CD4 Lymphocyte and Leukocyte Response to Vicriviroc (VCV) in 282 HIV-Infected Treatment-Naive and Experienced Subjects: Pooled Data from 4 Randomized Clinical Trials

CCR5

G. FATKENHEUER ¹, C. HOFFMANN ², A. SANSONE-PARSONS ³, W. GREAVES ³, L. DUNKLE³;
¹Univ. Cologne, Cologne, Germany, ²Univ. Kiel, Kiel, Germany, ³Schering Plough, Kenilworth, NJ.

Background: VCV is a CCR5 antagonist currently in development for treatment of HIV. While these agents are potent inhibitors of HIV, they also block chemokine binding and receptor signaling, which could have immunomodulatory effects. Here we evaluated the immunologic profiles of HIV-infected subjects following VCV treatment to assess its effect on peripheral lymphocyte populations. Methods: Complete differential blood counts, including absolute CD4 and %CD4 were measured in 282 HIV-infected subjects enrolled in 4 independent trials. Subjects received a range of VCV doses for 2-48 weeks, either as monotherapy or in combination with an optimized background or Combivir^®. Results for all subjects with values at baseline (BL) and the reported interval are presented. Results: BL differential blood counts and absolute and %CD4 were similar across studies. Change from BL in absolute CD4, %CD4, and WBC counts at 24 and 48 weeks are shown in the Table. There was no clinically significant impact on WBC, lymphocytes, or neutrophils during follow-up. As expected in ARV-treated patients, there was a substantial and sustained improvement in CD4 with VCV; this was greater than was seen with control. There was no apparent increase in infections with VCV relative to control.
Mean change from BL at 24 and 48 weeks

	VCV 5 mg*	VCV 10 mg*	VCV 15 mg*	Control
Week 24 Abs CD4	n=43 +98.4	n=47 +130.2	n=48 +143.9	n=46 +43.4
% CD4	+4.9	+5.8	+5.7	+3.8
WBC	+1.2	+0.25	+0.75	-0.1
Week 48 Abs CD4	n=25 +138.9	n=28 +191.5	n=32 +158.9	n=32 +36.6
% CD4	+3.2	+6.3	+5.2	+2.7
WBC	+1.8	+0.8	+1.2	+0.2

*or equivalent of 25, 50, 75 mg in a non-ritonavir-containing regimen
Conclusions: VCV was associated with a durable improvement in CD4. In this group of studies, VCV had no adverse effect on WBC counts in HIV-1 infected patients, and was not associated with an increased risk of infections.