Presentation Abstract

Session: 97-New Antiretrovirals
Monday, Sep 13, 2010, 11:15 AM - 1:15 PM
Presentation Title: H-938a - Antiviral Effect of Vicriviroc (VCV) plus Ritonavir-Boosted Atazanavir (ATV/r) Similar to Tenofovir/emtricitabine (TEM) + ATV/r but Efficacy (%<50c/mL) Inferior as Initial Therapy
Location: Exhibit Hall B1
Poster Board Number: 402
Presentation Number: H-938a
Pres. Time: Monday, Sep 13, 2010, 11:15 AM - 1:15 PM
Category: H
Keywords: antiretroviral therapy ; CCR5 antagonist ; Vicriviroc 
Author(s): L. M. DUNKLE MD1, J. GATHE 2, H. ZHOU 1, M. MCCARTHY 1;
1Merck Res. Lab., KENILWORTH, NJ, 2Therapeutic Concepts, Houston, TX.
Financial Disclosures:  L. M. Dunkle,
Employee Role(s): Employee, Received: Salary.
J. Gathe,
Schering-Plough Research Institute Role(s): Consultant, Investigator, Received: Research Support, Consulting Fee.
H. Zhou,
Merck Research Laboratories Role(s): Employee, Received: Salary.
M. Mccarthy,
Merck Research Laboratories Role(s): Employee, Received: Salary.
Abstract: Background:
P04875, a global Phase 2 trial, explored a class-sparing regimen of VCV, a CCR5 antagonist, plus ATV/r vs TEM + ATV/r, as initial antiretroviral therapy, avoiding NRTI and NNRTI toxicity, lipid toxicity and cross-resistance to other PIs.
Methods:
CCR5-tropic HIV-infected treatment-naïve subjects were randomized 1:1 to open-label treatment: 95 in Stage 1, and 123 in Stage 2, following review of 24-week Stage 1 data by an external DSMB. The primary endpoint was antiviral activity (drop from baseline HIV RNA); key secondary endpoint was efficacy (%<50 copies/mL at 48 weeks).
Results:
Subjects were mean 37 yrs of age, 34% female, 44% non-white; 61% in US or EU. Mean baseline HIV RNA = 4.65 log10 c/mL; CD4 count = 316 cells/mL. Overall, 86% completed 48 weeks; 23% VCV vs 17% TEM discontinued prematurely (D/C). The only imbalanced reason for D/C was “adverse event” as judged by investigators (9 VCV vs 1 TEM), 7 of 10 during Stage 1.
Summary Statistics
Endpoint ParameterVCV
n=108
TEM
n=108
Mean Δ from B/L HIV RNA-2.43 log10-2.53 log10Difference: 0.16
(-.14, 0.46)
%<50 c/mL at 48 weeks76%83%OR: 0.62
(0.31, 1.22)
PDVF29 (8% )3 (3%)
Detection of D/M (R5/X4) virus3 (3%)1 (1%)
1Treatment effects for each endpoint were adjusted for baseline HIV RNA and CD4
2Protocol-defined virologic failure = inadequate response or rebound >50 c/mL from full suppression

Non-adherence was the apparent cause of 9/12 PDVF. No drug-resistance and few R5/X4 HIV strains were detected on drug. Adverse events among D/C were heterogeneous; there were no predominant AEs in the VCV group, and no difference between groups in laboratory abnormalities.
Conclusions:
In this trial, drop in viral load was similar between groups; PDVF was often due to non-adherence. When analyzed as failures, D/C (which may have been impacted by an open-label design) resulted in suppression rates in VCV arm suggesting lesser efficacy (%<50 c/mL). VCV+ATV/r, despite promising antiviral activity and safety, did not appear to meet the current standards of efficacy for initial therapy of HIV.




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