Articles
on Vicriviroc
CCR5
Antagonist Vicriviroc Demonstrates Long-Term
Safety and Efficacy at 96 Weeks
9/14/2009
Assessment
of Pharmacokinetic and Safety Interactions Between Vicriviroc
and CYP3A4 Substrates, Inhibitors, and Inducers
9/14/2009
Clonal
Analysis of the gp120 V3 Loop from Clinical Isolates Displaying Phenotypic Resistance
to Vicriviroc
9/14/2009
Vicriviroc
Long-term Safety and Efficacy: 96-Week Results from the VICTOR-E1 Study
9/14/2009
Comparison
of Phenotypic (TrofileŽ) and Genotypic
(SensiTrop II) Assays to Determine HIV Tropism in Treatment-Naīve Subjects
2/10/09
Comparison
of TrofileŽ and ViroTectTropism
Assays in Treatment-Experienced Subjects
2/10/09.
Rapamycin
Enhances Anti-HIV Activity of Experimental CCR5 Antagonist Vicriviroc
1/16/09
Long-term Safety of Vicriviroc
11/05/2008
Low
Doses of CCR5 Antagonist Vicriviroc Do Not Suppress
HIV as well as Efavirenz (Sustiva) in Treatment-naive Patients; New Study Underway
10/14/08
Schering-Plough
Initiates Phase II Study with Vicriviroc in
Treatment-naīve HIV-infected Patients
4/16/08
CCR5
Antagonist Vicriviroc Shows Continued Benefits
and Good Tolerability at 48 Weeks: VICTOR-E1 Trial
2/05/08
Vicriviroc,
a Next Generation CCR5 Antagonist, Exhibits Potent, Sustained Suppression of Viral
Replication in Treatment-Experienced Adults: VICTOR-E1 48-week Results.
2/10/08
Vicriviroc, a Next
Generation CCR5 Antagonist, Exhibits Potent, Sustained Suppression of Viral Replication
in Treatment-Experienced Adults: VICTOR-E1 48-week Results
2/05/08
Effect of Virus Concentration on in vitro Measurement
of Phenotypic Resistance to the CCR5 Antagonist Vicriviroc.
2/05/08
The Effect of Vicriviroc
Upon Viral Load in HIV/HCV Co-infected Patients Receiving a Ritonavir-containing
Protease Inhibitor Regimen.
2/05/08
Vicriviroc in Combination
Therapy With an Optimized Antiretroviral Regimen for Treatment-Experienced Subjects:
The VICTOR-E1 Trial.
2/05/08
Vicriviroc:
An Overview
Vicriviroc
is an oral CCR5 receptor antagonist in development by Schering-Plough. Vicriviroc
is a novel entry and fusion inhibitor that has shown promise in the treatment
of HIV patients who are resistant to enfuvirtide
(Fuzeon) and other antiretrovirals.
The US Food and Drug administration has granted fast-track approval status to
vicriviroc. Entry
and fusion inhibitors act differently than other classes of anti-HIV drugs (e.g.,
protease inhibitors, nucleoside reverse transcriptase inhibitors) by preventing
HIV from infecting and entering cells, rather than trying to eradicate HIV after
the virus has infected a cell.
 |
|
HIV-1 interacts with a cell-surface receptor, primarily
CD4, and through conformational changes becomes more closely associated with the
cell through interactions with other cell-surface molecules, such as the chemokine
receptors CXCR4 and CCR5. |
The
CCR5 receptor acts with the CD4 receptor on the surface of T cells to facilitate
entry of HIV into cells. Because previous research has suggested that individuals
who lack a functional CCR5 receptor are largely resistant to HIV infection, the
CCR5 receptor has been a target of investigation in development of anti-HIV therapy.
A
Phase II trial of vicriviroc in treatment-naive patients was discontinued in October
2005 because detectable viral levels returned in some patients taking the drug
with lamivudine/zidovudine compared to the control group taking efavirenz and
lamivudine/zidovudine. No significant adverse events contributed to the discontinuation.
Patients in this study will remain on vicriviroc until alternate regimens are
chosen with their physicians.
A
second Phase II trial in treatment-experienced patients will continue. The manufacturer
also plans to continue evaluating SCH-D in combination with other treatment regimens
in treatment-naive and -experienced patients.
Phase
I studies of SCH-D have evaluated 10 mg, 25 mg, and 50 mg tablets.
Researchers
have evaluated the immunologic profiles of HIV-infected subjects following VCV
treatment to assess its effect on peripheral lymphocyte populations. Complete
differential blood counts, including absolute CD4 and %CD4 were measured in 282
HIV-infected subjects enrolled in 4 independent trials. Subjects received a range
of VCV doses for 2-48 weeks, either as monotherapy or in combination with an optimized
background or Combivir®.
Results:
| VCV
5 mg* | VCV
10 mg* | VCV
15 mg* | Control | Week
24 Abs CD4 | n=43
+98.4 | n=47
+130.2 | n=48
+143.9 | n=46
+43.4 | %
CD4 | +4.9 | +5.8 | +5.7 | +3.8 | WBC | +1.2 | +0.25 | +0.75 | -0.1 | Week
48
Abs CD4 | n=25
+138.9 | n=28
+191.5 | n=32
+158.9 | n=32
+36.6 | %
CD4 | +3.2 | +6.3 | +5.2 | +2.7 | WBC | +1.8 | +0.8 | +1.2 | +0.2 | | *or
equivalent of 25, 50, 75 mg in a non-ritonavir-containing regimen |
|
VCV
was associated with a durable improvement in CD4. In this group of studies, VCV
had no adverse effect on WBC counts in HIV-1 infected patients, and was not associated
with an increased risk of infections.
Two-year
Follow up of Treatment-experienced Patients on Vicriviroc
VCV
demonstrated durable antiretroviral activity and CD4 response in treatment-experienced
(TE) subjects at 48 weeks (Gulick, IAS 2007 abstract 1623). Researchers presented
2-year data for TE patients who received VCV and participated in a roll-over study.
HIV-1 infected
subjects successfully completing the 48-week phase of ACTG 5211 could enter this
open-label multicenter study and receive VCV 15 mg in addition to previously optimized
background therapy (OBT) that included a ritonavir-boosted protease inhibitor.
Additionally,
subjects with a tropism shift to R5/X4 virus with HIV RNA ?1 log10 below baseline
and no decrease in CD4 count could enroll. We assessed change from baseline in
HIV RNA and CD4 in subjects who had ?12 months follow-up, as well as new opportunistic
infections (OIs); malignancies; seizures; and hepatotoxicity.
Results
Of
79 subjects entering the study, 54 had at least 12 months exposure to VCV. Data
were available for 39 subjects (data pending for 15 ongoing subjects): mean treatment
duration (from first dose in ACTG 5211 to last dose in the rollover protocol)
was 103 weeks (range 49-145).
Median
change in HIV RNA from baseline (ACTG 5211) was -2.2 log10; median change in CD4
count was +84 cells/mm3; 23/39 subjects (60%) had HIV-RNA <50 copies/mL and
28/39 (72%) had <400 copies/mL.
12
subjects discontinued: 2 due to adverse events, 6 for patient choice, 2 for administrative
reasons, and 2 for virologic failure. 6 tropism shifts occurred during the study:
2 to X4 and 4 to R5/X4.
Other
than pulmonary TB (n=1), no OIs, VCV-related hepatotoxicity, cardiovascular events,
seizures, or new lymphomas (since February 2006) were reported.
The
authors concluded that VCV, 15 mg qd, plus OBT was generally well tolerated and
provided potent and durable antiretroviral activity.
These
results represent the longest follow-up data available for a CCR5-containing regimen
to date.
11/12/07
Sources
National
Institutes of Health
US Food and Drug Administration
Vicriviroc is an experimental entry inhibitor developed by the Schering-Plough
Research Institute. Vicriviroc is also sometimes called SCH-D, its former code
name.
FDA-approved
Therapies for HIV and AIDS