Human immunodeficiency virus seroconversion and evolution of the hepatitisC virus quasispecies

When chronic hepatitis C virus (HCV) infections are complicated by acquisit ion of human immunodeficiency virus (HIV), liver disease appears to acceler ate and serum levels of HCV RNA may rise. We hypothesized that HIV might af fect the HCV quasispecies by decreasing both complexity (if HIV-induced imm unosuppression lessens pressure for selecting HCV substitutions) and the ra tio of nonsynonymous (d(N)) to synonymous (d(S)) substitutions, because d(N ) may be lower (if there is less selective pressure). To test this hypothes is, we studied the evolution of HCV sequences in 10 persons with chronic HC V infection who seroconverted to HIV and, over the next 3 years, had slow o r rapid progression of HIV-associated disease. From each subject, four seru m specimens were selected with reference to HIV seroconversion: (i) more th an 2 years prior, (ii) less than 2 years prior, (iii) less than 2 years aft er, and (iv) more than 2 years after. The HCV quasispecies in these specime ns was characterized by generating clones containing I kb of cDNA that span ned the E1 gene and the E2 hypervariable region 1 (HVR1), followed by analy sis of clonal frequencies (via electrophoretic migration) and nucleotide se quences. We examined 1,320 cDNA clones (33 per time point) and 287 sequence s (median of 7 per time point). We observed a trend toward lower d(N)/d(S) after HIV seroconversion in 7 of 10 subjects and lower d(N)/d(S) in those w ith rapid HIV disease progression. However, the magnitude of these differen ces was small. These results are consistent with the hypothesis that HIV in fection alters the HCV quasispecies, but the number of subjects and observa tion time may be too low to characterize the full effect.