Mechanism of Action: HIV-1 entry inhibitor. Vicriviroc is a reversible, small-molecule CCR5 co-receptor antagonist that prevents viral entry by binding to a domain of CCR5 and subsequently inhibiting the interaction between HIV-1 gp120 and CCR5.4,5,6
T1/2: 28 hours (vicriviroc 50 mg twice daily in HIV-infected individuals).4
Metabolism/Elimination: Vicriviroc is primarily metabolized by cytochrome P450 (CYP) 3A4 and, to a lesser extent, by CYP3A5 and CYP2C9.4 Approximately 47% and 45% of a single 14C-radiolabeled dose of vicriviroc in healthy subjects is excreted in urine and in feces, respectively.7
Resistance: Isolates from treatment-experienced participants experiencing virologic failure in two Phase III trials were analyzed. Analysis included only those subjects with R5-tropic virus detected at baseline. Seventy-one out of 486 vicriviroc-treated participants met the protocol-defined virologic failure criteria after 48 weeks of treatment. Of those virologic failures, 10% were determined to have dual-mixed/X4 virus at the time of failure. Resistance to vicriviroc was identified in 1% of treated participants (4 out of 486). Clonal analysis identified 2 to 5 amino acid substitutions in the V3 loop associated with vicriviroc resistance; changes outside the V3 loop were also seen in resistant clones; however, no consistent pattern was observed.8
Phase II (treatment-naive):
Phase III (treatment-experienced) (two identically designed trials, VICTOR-E3 and VICTOR-E4):
In the Phase III trials VICTOR-E3 and VICTOR-E4, vicriviroc was comparable to placebo in terms of adverse events, with no significant differences in new AIDS diagnoses, malignancies, or other major adverse events. Study discontinuations due to adverse events occurred in 14% of participants receiving vicriviroc and in 8% of participants receiving placebo.14
In a Phase II trial comparing vicriviroc and emtricitabine/tenofovir DF, each combined with ritonavir and atazanavir, a greater proportion of vicriviroc participants than emtricitabine/tenofovir DF participants discontinued treatment because of adverse events. There were no predominant adverse events among vicriviroc-treated participants. Laboratory abnormalities were comparable between both groups.11
Vicriviroc is a substrate of CYP3A4; however, it is neither a CYP3A4 inhibitor nor inducer.15
If carbamazepine or rifabutin (CYP3A4 inducers) are co-administered with vicriviroc in a regimen containing a ritonavir-boosted protease inhibitor, the ritonavir dose should be increased. Rifampin (CYP3A4 inducer) co-administered with vicriviroc is not recommended.15
No vicriviroc dosage adjustments are required when vicriviroc is co-administered with most ritonavir-boosted protease inhibitors.4
There are no significant drug interactions between vicriviroc and the drugs lamivudine, zidovudine, or tenofovir. Efavirenz significantly increases the metabolism of vicriviroc; however, the addition of ritonavir in the regimen attenuates the inductive effects.4
Vicriviroc alone has minimal effects on the pharmacokinetics of ethinyl estradiol (EE) or norethindrone (NET). Ritonavir administered alone or with vicriviroc, however, is associated with decreases in EE and NET exposure.16
1. United States National Library of Medicine. ChemIDplus Advanced. Last accessed on November 13, 2013.
2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Last accessed on November 13, 2013.
3. Dunkle LM. Merck Research Laboratories. Vicriviroc Discontinued Investigator Letter. National AIDS Treatment Advocacy Project (NATAP): News Updates; 2010. Last accessed on November 13, 2013.
4. Brown KC, Paul S, Kashuba AD. Drug interactions with new and investigational antiretrovirals. Clin Pharmacokinet. 2009;48(4):211-41. Last accessed on November 13, 2013.
5. Emmelkamp JM, Rockstroh JK. CCR5 antagonists: comparison of efficacy, side effects, pharmacokinetics and interactions--review of the literature. Eur J Med Res. 2007 Oct 15;12(9):409-17. Last accessed on November 13, 2013.
6. Strizki JM, Tremblay C, Xu S, et al. Discovery and characterization of vicriviroc (SCH 417690), a CCR5 antagonist with potent activity against human immunodeficiency virus type 1. Antimicrob Agents Chemother. 2005 Dec;49(12):4911-9. Last accessed on November 13, 2013.
7. Kasserra C, O'Mara E. Pharmacokinetic Interaction of Vicriviroc with Other Antiretroviral Agents: Results from a Series of Fixed-Sequence and Parallel-Group Clinical Trials. Clin Pharmacokinet. 2011 Apr;50(4):267-80. Last accessed on November 13, 2013.
8. McNicholas P, Vilchez RA, Greaves W, et al. Detection of HIV-1 CXCR4 tropism and resistance in treatment experienced subjects receiving CCR5 antagonist-Vicriviroc. J Clin Virol. 2012 Oct;55(2):134-9. Last accessed on November 13, 2013.
9. Schürmann D, Fätkenheuer G, Reynes J, et al. Antiviral activity, pharmacokinetics and safety of vicriviroc, an oral CCR5 antagonist, during 14-day monotherapy in HIV-infected adults. AIDS. 2007 Jun 19;21(10):1293-9. Last accessed on November 13, 2013.
10. Merck. Efficacy and Safety of VICRIVIROC in HIV-Infected Treatment-Naïve Subjects. Bethesda (MD): National Library of Medicine (US). Registered on October 29, 2007. NLM Identifier: NCT00551018. Last accessed on November 13, 2013.
11. Dunkle LM, Gathe J, Zhou H, McCarthy M. 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. Abstract presented at: 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 12-15, 2010; Boston, MA. Abstract H-938a. Last accessed on November 13, 2013.
12. Schering-Plough. Vicriviroc in Combination Treatment With an Optimized ART Regimen in HIV-Infected Treatment-Experienced Subjects (VICTOR-E3). Bethesda (MD): National Library of Medicine (US). Registered on August 30, 2007. NLM Identifier: NCT00523211. Last accessed on November 13, 2013.
13. Schering-Plough. Vicriviroc in Combination Treatment With an Optimized ART Regimen in HIV-Infected Treatment-Experienced Subjects (VICTOR-E4). Bethesda (MD): National Library of Medicine (US). Registered on May 15, 2007. NLM Identifier: NCT00474370. Last accessed on November 6, 2013.
14. Mascolini M. Vicriviroc Does Not Outdo Placebo Regimen in Phase 3 Trials. Conference Reports for National AIDS Treatment Advocacy Project (NATAP): 17th Conference on Retroviruses and Opportunistic Infections (CROI); February 16-19, 2010; San Francisco, CA. Last accessed on November 13, 2013.
15. Kasserra C, O’Mara E, Lisbon E. Assessment of Pharmacokinetic and Safety Interactions Between Vicriviroc and CYP3A4 Substrates, Inhibitors, and Inducers. Abstract presented at: 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 12-15, 2009; San Francisco, CA. Abstract H-230. Last accessed on November 13, 2013.
16. Kasserra C, Li J, March B, O'Mara E. Effect of vicriviroc with or without ritonavir on oral contraceptive pharmacokinetics: a randomized, open-label, parallel-group, fixed-sequence crossover trial in healthy women. Clin Ther. 2011 Oct;33(10):1503-14. Last accessed on November 13, 2013.
Last Reviewed: November 13, 2013
Last Updated: November 13, 2013