1068 
The Effect of Vicriviroc upon HCV Viral Load in HIV/HCV-co-infected Patients Receiving a Ritonavir-containing Protease Inhibitor Regimen
Gerd Fatkenheuer*1, C Hoffmann2, J Slim3, R Rouzier4, A Sansone-Parsons5, M Treitel5, C Kasserra5, A Keung5, E O'Mara5, and D Schurmann6
1Univ of Cologne, Germany; 2Univ Kiel, Germany; 3St Michael`s Med Ctr, Newark, NJ, US; 4CentreCap, Montpellier, France; 5Schering-Plough Res Inst, Kenilworth, NJ, US; and 6Med Univ of Berlin, Germany
Background: Inhibition of HIV entry by CCR5
antagonists is a new strategy currently being studied for treatment of HIV
infection. As CCR5 is present on a variety of immune cells (e.g., CD8+
cells), the effect of CCR5 inhibition on the HCV viral load of patients co-infected
with HIV/hepatitis C virus (HCV) was studied.
Methods: Co-infected patients, whose HIV was stable
(<400 copies/mL) on a ritonavir (RTV) -containing protease inhibitor (PI) ART
were enrolled into this randomized, double-blind, placebo controlled multi
center study: 40 subjects were scheduled to receive 5 mg, 10 mg, 15 mg
vicriviroc (VCV) once, or placebo for 28 days in addition to their stable
background therapy. Safety was the primary objective of this study, and
pharmacokinetics was a secondary objective. Clinical examination and laboratory
tests were conducted throughout the study. An intention-to-treat analysis was
performed including all randomized subjects with HCV RNA at all time points as
the primary parameter.
Results: The study was closed after enrollment of 28
subjects (18 men, 10 women) of whom 24 (86%) were Caucasian. Subjects had a
median (range) baseline age of 42 (25 to 56) years of age and a CD4+
cell count 436 (128 to 1240)/µL. No substantive changes from baseline HCV RNA
levels were noted over the course of the study between VCV or placebo treated
patients (see the figure). Adverse events were equally distributed among
placebo and VCV arms and were generally mild (headache, diarrhea). Transient
elevations of alanine aminotransferase (ALT), aspartate aminotransferase (AST),
or gamma-glutamyl transferase (GGT) occurred in 4 patients on treatment (3 VCV,
1 placebo), 2 of which were considered clinically significant (1 VCV 10 mg, 1
placebo). pharmacokinetic parameters (Cmax, Cmin, AUC) of
VCV were dose-dependent and comparable to healthy volunteers.
Conclusions: This was the first study of a CCR5
antagonist in patients with HIV and HCV co-infection. No clinically meaningful
changes in HCV viral load were observed in stable co-infected patients
receiving VCV in combination with a RTV-containing PI regimen. VCV in combination
with background therapy was safe and well tolerated when administered for 28
days.
Mean change in HCV viral load in VCV- and placebo-treated
patients
(VCV=  ,
PBO =  )
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