Several
HCV protease inhibitors are currently under development for the treatment of chronic
hepatitis C. In vitro studies have identified mutations in HCV replicon systems
that confer resistance to
telaprevir (VX-950) and SCH503034.
Italian investigators
conducted an analysis of mutations within the NS3 protease gene of genotype 1
HCV in 38 HIV-HCV coinfected patients.
While 19 patients were receiving HIV
protease inhibitors (PIs) at the time of sample collection, the remaining
19 had not received anti-HIV therapy containing PIs for the prior 2 years. These
subsets of patients were analyzed separately. The authors also compared samples
from the HIV-infected group with a pool of 250 NS3 protease sequences obtained
from Genbank.
Results
Amino acid changes at position 156 (A --> T or G), conferring resistance to
HCV PIs, were significantly more frequent among HIV positive patients than in
the control group: 3 of 38 (7.8%) vs 2 of 250 (0.8%); P = 0.02].
While HIV-infected patients without exposure to HIV PIs had a similar prevalence
of NS3 mutations compared to the control group (0 of 19 [0%] vs 2 of 250 [0.8%];
P = non-significant), those receiving HIV PI had mutations significantly more
often than the control group (3 of 19 [15.8%] vs 2 of 250 [0.8%]; P = 0.003).
However, differences in the prevalence of mutations at NS3 position 156 between
HIV-infected patients exposed or not exposed to HIV PIs did not achieve statistically
significance (3 of 19 [15.8%] vs 0 of 19 [0%]; P = non-significant), probably
due to the small sample size.
Amino acid substitutions at NS3 position 170 (V --> L, Y, E, F or T) were more
often found in HIV-infected patients than in the control group from Genbank (5
of 38 [13%] vs 0 of 250 [0%]; P < 0.0001].
Mutations at this position occurred at comparable rates among HIV-infected patients
exposed or not exposed to HIV PIs (2 of 19 [10.5%] vs 3 of 19 [15.7%]; P = non-significant).
The
researchers concluded that "in this small cohort of HIV-HCV coinfected patients,
the natural strains of the NS3 protease domain exhibited mutations that were related
to resistance to [HCV PIs]. This finding could have implications for the treatment
with [HCV PIs] of HIV/HCV coinfected patients".
Further
studies are needed to better define the clinical significance of these interesting
findings.
11/14/06
Reference G
Morsica, S Bagaglio, L Alagna, and others. Mutations in the Natural Strains of
NS3 Protease Domain of HCV in HIV/HCV Coinfected Patients Under Antiretroviral
Therapy Including or Not HIV Protease Inhibitors. 57th AASLD. Boston, MA. October
27-31, 2006. Abstract 436.
Amino acid changes at position 156 (A --> T or G), conferring resistance to
HCV PIs, were significantly more frequent among HIV positive patients than in
the control group: 3 of 38 (7.8%) vs 2 of 250 (0.8%); P = 0.02]. 
