Articles
on Vicriviroc
Experimental
CCR5 Antagonist Vicriviroc
Appears Safe and Well Tolerated in HIV/HCV Coinfected
Patients
1/12/2010
CCR5 Antagonist
Vicriviroc Demonstrates
Greater Efficacy in Patients Identified Using More
Sensitive CCR5 Tropism Test
1/12/2010
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 Trofile® 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-naïve 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
