Vicriviroc is a CCR5 antagonist under development by Schering Plough. It was previously known as SCH-D and as SCH-417690.

A dose-escalated 14-day study of vicriviroc monotherapy has been carried in 48 patients, comparing doses of 10, 25 and 50mg twice daily to placebo (Schurmann 2004). Vicriviroc caused a maximal viral load reduction of 1.5 log₁₀ in the 50mg group. Ten days after the end of the trial, viral load was still more than 0.5 log₁₀ below baseline in the 50mg group. This long-term effect is likely to be explained by the prolonged saturation of CCR5 receptors on T-cells (Schurmann 2004).

Because of its long half-life, vicriviroc is likely to be a once daily product. Its levels can be boosted if it is taken alongside ritonavir

Vicriviroc was well tolerated: only one adverse event (a fever) was reported during the study that might have a link to the drug.

Some researchers are concerned that over time, use of CCR5 antagonists will favour the emergence of more lethal viruses that use the CXCR4 receptor. Viruses that favour the CXCR4 receptor are known to infect and kill CD4 T-cells much more rapidly than CCR5 viruses. In this study, one patient with viral load reduction of greater than 1.5 log₁₀ had evidence of a transient switch to CXCR4 virus after treatment.

Despite the optimism surrounding this drug, Schering Plough announced in October 2005 that a phase II trial of vicriviroc in 93 treatment-naive patients was halted due to early viral rebound. Although a study in treatment-experienced patients is continuing, the future of vicriviroc remains uncertain.

Key research

Schurmann (2004) randomised 48 patients to receive 10, 25 or 50mg vicriviroc twice daily or placebo. All participants had been off antiretroviral therapy for at least 8 weeks prior to starting vicriviroc treatment. Mean viral load was 81,100 copies/ml in the placebo group, 36,300 copies/ml in the 10mg group, 43,700 copies/ml in the 25mg group and 106,000 copies/ml in the 50mg group. CD4 cell counts ranged from 369 to 486/mm³. The maximum viral load reduction occurred in the 50mg group: by day 15, viral load had fallen by a mean of 1.5 log₁₀, compared to 1 log₁₀ copies/ml in the 10mg group and no change from baseline in the placebo group. However, the proportions who achieved a viral load reduction of greater than 1.5 log₁₀ was similar in the 25 and 50mg groups (46 vs. 45%). There was only 1 adverse event possibly related to the drug (fever).

Reference

Schurmann D et al. SCH D: antiviral activity of a CCR5 receptor antagonist. Eleventh Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 140LB, 2004.