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Background:  We tested the hypothesis that HIV infection and immune suppression alter the host-hepatitis C virus (HCV) interaction, resulting in fewer amino acid changing substitutions in viral variants. Accelerated liver disease progression and higher HCV RNA levels have been reported in persons co-infected with HIV compared with HCV infection alone. If this interaction is dependent on reduced immune selective pressure, then a reduced rate of nucleotide changes that result in amino acid replacements (nonsynonymous changes, d_N), would be expected

Methods:  Subjects participating in a longitudinal study of the natural history of HCV infection underwent semiannual standardized interviews and phlebotomy for HIV and HCV RNA testing. We chose for study of HCV sequence evolution the first and most recent stored specimens of HCV-infected (genotype 1a or 1b) HIV-negative subjects (group 1), HIV-positive subjects with persistently high (> 350 cells/mm³; group 2), or low (< 200 cells/mm³, group 3) CD4⁺ counts. For HCV quasi-species analysis, RNA was extracted from serum, and amplified using RT-PCR. After alignment and trimming to equal length, direct sequencing of amplified products yielded 613 nucleotides spanning portions of the HCV E1 and E2 envelope regions including the first hypervariable region (HVR1). Overall genetic distances were corrected using the Kimura method, and d_N was calculated using the method of Nei and Gojobori. Median values for the 3 groups were compared using nonparametric analysis of variance; p values < 0.05 were considered significant.

Results:  A total of 79 subjects (59 men, 20 women; 7 white, 19 black, 53 Hispanic, mean age 45.6 years) were evaluable:  38 in group 1, 21 in group 2, and 20 in group 3. Overall median rate of change was 0.47 changes per hundred residues per year (range, 0 to 8.6), and at nonsynonymous sites was 0.33 (0 to 4.7). A trend toward lower genetic distance in group 3 was not statistically significant after correction for the sampling interval. Likewise, median d_N and rate of d_N tended to be lower for persons in group 3, but these differences were not significant.

Conclusions:  In this study of a predominantly Hispanic sample, HCV envelope sequences obtained at 2 visits 2 to 3 years apart showed substantial evolution, with a trend toward reduced change in persons with more profound immunosuppression. However, variability between groups was not significantly greater than variation within groups.

Keywords: HCV; Coinfection; Evolution