"A total of 118 heavily treatment-experienced HIV patients (median viral load 36,380 copies/ml and CD4 146 cells/microliter) with R5-type virus taking ritonavir-boosted PI-containing regimens were randomized in the double-blind, 48-week study. Change in viral load after addition of vicriviroc (5, 10 or 15 mg) dosed once daily (QD) or placebo was measured at 14 days, and then at 12 and 24 weeks, after the background antiretroviral regimen had been optimized at day 14.

"At day 14, the primary endpoint of the study, the mean HIV-1 RNA change from baseline (log10 copies/mL) for the vicriviroc 5, 10 and 15 mg QD arms were decreases of -0.87, -1.15 and -0.92, respectively, compared to an increase of +0.06 for the placebo arm.

"At week 24, the mean HIV-1 RNA change (log10 copies/mL) for vicriviroc 5, 10 and 15 mg QD arms were declines of -1.51, -1.86 and -1.68, respectively, compared to a decrease of -0.29 for the placebo arm. Mean CD4 cell counts increased at week 24 for the vicriviroc 5, 10 and 15 QD mg arms by +84, +142 and +142 respectively, compared to a decrease of -9 for the placebo group.

"Emergence of detectable X4-type virus was detected in 8 (27 percent), 3 (10 percent) and 2 (7 percent) of patients in the vicriviroc 5, 10 and 15 QD mg arms, compared to 1 (4 percent) in the placebo arm. Five of the 8 patients in the 5 mg QD arm demonstrated the emergence of X4 virus prior to optimization of their background regimen.

"The 5 mg QD dose of this trial was discontinued early due to suboptimal efficacy (patients were dose-escalated to 15 mg QD) and the study as a whole was unblinded in March 2006 after recommendation from the Study Monitoring Committee, based on reports of five malignancies (two Hodgkin's disease, one with prior Hodgkin's disease; two non-Hodgkin's disease, one with prior Hodgkin's disease; and one gastric adenocarcinoma) among vicriviroc recipients.

"The ACTG (including an independent safety monitoring committee) concluded causal association between vicriviroc and the malignancies could not be determined by this study. Coupled with evidence of significant virologic activity and CD4 count increases, a decision was made to continue the trial with the 10 and 15 mg doses.

"Open-label follow-up of patients continues; the median length of study treatment at the time of this analysis was more than 40 weeks for the 10 and 15 mg vicriviroc treatment groups.

"Based on the ACTG study reported above and extensive pharmacokinetic and pharmacodynamic data, Schering-Plough Research Institute has initiated a new Phase II clinical trial of higher doses of vicriviroc in treatment-experienced HIV patients, with the goal of achieving incremental improvement in viral suppression.

"VICTOR-E1 (Vicriviroc in Combination Treatment with Optimized Antiretroviral Treatment Regimen in Experienced Subjects) will evaluate the safety and efficacy of vicriviroc (20 mg and 30 mg once daily) compared to placebo in combination with an optimized ritonavir-boosted, protease inhibitor-containing antiretroviral regimen.

"The primary objective of the study is to evaluate the antiviral activity of vicriviroc as measured by the decline of viral load (log10 copies/mL) from baseline at 12 and 24 weeks. A total of 120 patients who are currently failing an antiretroviral treatment regimen will be enrolled in the 48-week trial. The study is being conducted at sites throughout Europe and North and South America.

"For additional information on the ongoing VICTOR-E1 trial and trial sites, please visit http://www.clinicaltrials.gov."