 |
|
|
| |
Vicriviroc Troughs Correlate With Response in VICTOR-E1 Salvage Study
|
| |
| |
9th International Workshop on Clinical Pharmacology of HIV Therapy
April 7-9, 2008
New Orleans
Mark Mascolini
Reaching a vicriviroc trough concentration above 100 ng/mL made a good 48-week virologic response more likely in the VICTOR-E1 trial, regardless of whether people took 20 or 30 mg of this CCR5 antagonist [1]. But people who took 30 mg once daily were more likely to keep their trough above 100 ng/mL.
VICTOR E1 randomized patients with triple-class experience and one or more primary reverse transcriptase and protease mutations to 20 or 30 mg of vicriviroc daily or to placebo plus an optimized background regimen of other antiretrovirals [2]. Everyone had CCR5-using virus when the study began, and everyone took a ritonavir-boosted protease inhibitor with vicriviroc.
In a 48-week time-to-loss-of-virologic-response analysis, people with a pretreatment viral load below 100,000 copies were more likely to reach a load below 50 copies with 30 mg of vicriviroc (70%) or 20 mg of vicriviroc (64%) than with placebo (32%). Reaching a sub-50 load was much less likely when the pretreatment load lay above 100,000 copies--33% got under 50 copies with 30 mg of vicriviroc, 17% with 20 mg, and 10% with placebo.
Study participants who took 30 mg of the CCR5 antagonist had a 46% higher median vicriviroc area under the concentration-time curve (AUC) than people taking 20 mg (5687 versus 3896 ng/h/mL). Schering investigators suggested this difference may partly explain why patients with a higher baseline viral load or fewer active drugs in their background regimen responded better to 30 mg of vicriviroc than to 20 mg. Median vicriviroc trough concentrations were 43% higher with 30 mg than with 20 mg (202 versus 141 ng/mL).
Because vicriviroc troughs correlated tightly with AUC, the investigators proposed that troughs (which require only one measurement) can replace AUC (which require several) when evaluating virologic response to vicriviroc. Among study participants whose trough exceeded 100 ng/mL, 58% had a 48-week viral load below 50 copies, compared with 30% whose trough lay at or below 100 ng/mL. Respective proportions who had a 48-week viral load under 400 copies/mL were 65% and 40%. Schering plans more detailed analyses to confirm 100 ng/mL as a reliable cutoff for response to vicriviroc.
While 90% of people taking 30 mg of vicriviroc had a trough above 100 ng/mL, 83% taking 20 mg had a trough that high. Drugs in the background regimen--which included darunavir, tipranavir, enfuvirtide, and tenofovir--did not affect vicriviroc troughs. Phase 3 vicriviroc trials use the 30-mg dose.
(Many complete slide sets and posters from this workshop will be available at www.hivpresentation.com shortly after the meeting ends.)
References
1. Keung A, Li C, Fellows K, et al. The pharmacodynamic correlation between vicriviroc plasma levels and virologic suppression. 9th International Workshop on Clinical Pharmacology of HIV Therapy. April 7-9, 2008. New Orleans. Abstract O20.
2. Zingman B, Suleiman J, DeJesus E, et al. Vicriviroc in combination therapy with an optimized ART regimen for treatment-experienced subjects: VICTOR-E1. 15th Conference on Retroviruses and Opportunistic Infections. February 3-6, 2008. Boston. Abstract 795.
|
| |
|
|
|
|
|
