Australasian Society for HIV Medicine

Results of VICTOR-E1 study (1,2) were presented at 15th Conference on Retroviruses and Opportunistic Infections (CROI). The final results of this Phase II clinical study showed that vicriviroc, the investigational CCR5 antagonist, demonstrated potent and sustained viral suppression through 48 weeks of therapy in treatment-experienced HIV-infected patients. Vicriviroc was administered once-daily as a single tablet in combination with an optimised ritonavir-boosted protease inhibitor containing antiretroviral regimen. Vicriviroc is a next-generation extracellular inhibitor of HIV infection designed to block entry of infectious virions into uninfected CD4 cells via antagonism of the CCR5 co-receptor.

Researchers reported the data in a late-breaker oral presentation at the Conference on 4 February. In the study, significantly more patients who added vicriviroc 30 mg once daily to a new optimised background therapy (OBT) had fully suppressed HIV-RNA (less than 50 copies/ml) at 48 weeks compared to patients receiving new OBT alone (56% vs. 14%, p=0.0002).

The study, known as VICTOR-E1 (Vicriviroc in Combination Treatment with Optimized Antiretroviral Therapy Regimen in Experienced Subjects), evaluated the safety and efficacy of vicriviroc (30 mg or 20 mg once daily) in combination with an optimised ritonavir-boosted, protease inhibitor-containing antiretroviral regimen compared to a control group receiving new OBT alone. The primary endpoint of the study was change in HIV-RNA at week 48. A total of 116 treatment-experienced adult HIV-infected patients with R5-type virus at screening were randomised in this placebo-controlled, double-blind study at 37 sites throughout Europe, South Africa and North and South America.

Results of the study through 48 weeks demonstrated potent and sustained viral suppression in the vicriviroc arms, with significantly greater decreases in mean HIV-RNA, as well as greater increases in mean CD4 counts, compared to the control arm. At 48 weeks, patients in the 30 mg and 20 mg vicriviroc treatment groups achieved mean decreases from baseline in viral load of -1.77 and -1.75 (log10 copies/mL), respectively, compared to -0.79 for the control group (p=0.0017 and p=0.0026, respectively). Mean increases from baseline in CD4 cell counts in the vicriviroc groups were +102 and +134 (cells/mm3), respectively, compared to +65 in the control group. Fewer patients in the vicriviroc groups discontinued from the study due to virologic failure compared to those in the control group (13% and 8% vs. 38%, respectively).

No clinically relevant differences in safety profile between the vicriviroc and control groups were observed in this study, including liver toxicity, opportunistic infections, malignancies or other conditions. There were no cases of grade 3/4 elevated ALT reported in the vicriviroc groups compared to one case in the control group, and there were one, two and one cases of grade 3/4 elevated total bilirubin reported among atazanavir recipients in each of the groups, respectively. There were no opportunistic infections reported in the vicriviroc groups compared to two in the control group, and no systemic malignancies reported in any of the groups in the 48-week study.

These results supported the selection of the 30 mg once-daily vicriviroc dose for use in ongoing Phase III clinical studies. The study is reviewed by Thaczuk (3).

Vicriviroc Ongoing Phase III Studies
Building on the results of the VICTOR-E1 study, Schering-Plough is currently enrolling patients in two large global Phase III clinical studies with vicriviroc administered once-daily as a single 30 mg tablet in adult treatment-experienced HIV patients with R5-type virus only. The two ongoing Phase III studies, known as VICTOR-E3 and VICTOR-E4 (Vicriviroc in Combination Treatment with an Optimised Antiretroviral Therapy Regimen in HIV-Infected Treatment-Experienced Subjects), evaluate the virologic benefit of adding vicriviroc 30 mg once daily to an optimised background therapy compared to a control group receiving new optimised background therapy alone. The optimised background therapy must include at least two drugs to which the patient's HIV is susceptible. Patients coinfected with hepatitis B or C may be included in these studies and there are no exclusions of commonly prescribed drugs or need for dose adjustments based on the known vicriviroc drug-drug interaction profile. The two studies are currently enrolling approximately 375 patients each at more than 160 sites in North America, Latin America, Europe, Australia and South Africa. For more information about the VICTOR-E3 and VICTOR-E4 clinical studies use link 2 and 3.

References and links

(1) Zingman B et al. Vicriviroc, a next generation CCR5 antagonist, exhibits potent, sustained suppression of viral replication in treatment-experienced adults: VICTOR-E1 48-week results. Fifteenth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 39LB, 2008.

(2) Zingman B et al. Vicriviroc in combination therapy with an optimized ART regimen for treatment-experienced subjects: VICTOR-E1. Fifteenth Conference on Retroviruses and Opportunistic Infections, Boston, poster abstract 795, 2008.

(3) Thaczuk D (2008) CROI: Vicriviroc appears safe and effective at higher doses in treatment-experienced patients after 48 weeks Aidsmap news Tuesday, February 05. Link to review: http://www.aidsmap.com/en/news/9DA77736-AB60-4373-B9F3-F7377D37867B.asp

(4) Information about the VICTOR-E3 Link to source:
http://clinicaltrials.gov/ct2/show/NCT00523211?term=vicriviroc&rank=4

(5) Information about the VICTOR-E4 clinical studies. Link to source:
http://clinicaltrials.gov/ct2/show/NCT00474370?term=vicriviroc&rank=5

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