HCV Quasispecies Association with Early Treatment Response in Singly and Coinfected Patients with Inherited Bleeding Disorders

Hepatitis C virus (HCV) quasispecies emergence has been linked to disease progression in patients with inherited bleeding disorders. Quasispecies selection in the setting of treatment intervention in HCV-HIV coinfected patients with PEG-IFN + ribavirin has not been described.

Patients with inherited bleeding disorders infected with HCV or HIV-HCV from 4 tertiary centers were enrolled in a NIH-sponsored treatment trial. All were given PEG-IFN alfa 2a (180mcg qw) + ribavirin (800mg qd). HCV viral loads (VL) were measured at baseline and weeks 2 and 4 (Roche COBAS Amplicor Monitor).

Quasispecies emergence was determined at the same timepoints via a heteroduplex complexity assay.

Results

Nineteen patients with inherited bleeding disorders were evaluated (17 male, 2 female). 42% (8/19) had HIV. Mean age was 38 years. 63% of patients were HCV genotype 1.

Six coinfected pts had baseline HIV RNA <75 copies/mL. Median log HCV VL at baseline were 5.84 and 6.37 IU/mL, for monoinfected vs. coinfected, respectively (p = n.s.). Median baseline CD4+ counts were 819 and 720 cells/mm3, respectively (p = n.s.).

The mean numbers of quasispecies at baseline were 1.8 (SE 0.29) and 2.8 (SE 0.22), respectively (p = 0.01). 50% of monoinfected patients achieved HCV VL below detectable limits (<600 IU/mL) during the 4-week period in contrast to 12.5% of the coinfected patients (p = 0.15).

Quasispecies number in both groups decreased with time, trending toward statistical significance (p = 0.07).

Multivariate analysis determined that a lower quasispecies count at baseline (1-2) was significantly associated with the probability of clearance (p < .0001) after controlling for genotype, HIV infection, age, gender, and CD4+ count.

Conclusions

·  HIV-HCV coinfected patients had greater HCV quasispecies complexity than monoinfected patients at baseline;

·  Treatment reduces quasispecies complexity over time;

·  These data suggest that failure to clear virus may be associated with increased baseline quasispecies complexity in patients with inherited bleeding disorders.

05/21/04

Reference
K E Sherman and others. HCV Quasispecies Association with Early Treatment Response in Singly and Coinfected Patients with Inherited Bleeding Disorders. Abstract 81 (oral). Digestive Disease Week 2004. May 15-20, 2004. New Orleans, LA.