Proteome-wide anti-hepatitis C virus (HCV) and anti-HIV antibody profiling for predicting and monitoring the response to HCV therapy in HIV-coinfected patients

Abstract

We quantified antibody responses to the hepatitis C virus (HCV) proteome that are associated with sustained virologic response (SVR) in human immunodeficiency virus (HIV)/HCV-coinfected patients treated with pegylated interferon and ribavirin. Analysis of pre- and posttreatment samples revealed significant decreases in the combined anti-core, anti-E1, and anti-NS4 HCV antibody titers in those with SVRs but not in those who experienced relapse or who did not respond. Furthermore, anti-HIV p24 antibody titers inversely correlated with treatment response. These results suggest that profiling anti-HCV antibody is useful for monitoring HCV therapy, especially in discriminating between those who experience relapse and those who have SVRs at 48 weeks.

Figures

Figure 1

Baseline antibody titers to HCV antigens and p24. A. Heat map representation of patient antibody profiles to the 6 HCV antigens in pretreatment samples from HIV-HCV coinfected patients with differing response to HCV therapy. Antibodies titers were determined in patients from 3 subgroups of HCV-HIV coinfected patients including NR (N=11), RELAP (n=9), SVR (n=9) and 2 non-infected controls. The antibody levels for each serum were log10 transformed and then the levels were color-coded as indicated by the log10 scale on the right, in which signal intensities range from red to green indicating high (red) and low (green) antibody titers. The unusual NR patient without anti-core, anti-E1 and anti-E2 antibodies is shown by the asterisk. B. Anti-p24 antibody titers. Each symbol represents individual samples from NR, RELAP and SVR subgroups. Antibody titers are plotted in LU on the Y-axis and the mean with 95% confidence interval are shown for each group. P values were calculated using the Mann Whitney U test.

Figure 2

Informative antibody titers pre- and post- HCV treatment in HIV-coinfected NR, RELAP and SVR subgroups. Anti-core, E1 and NS4 antibodies levels at baseline and post-treatment in individual patients from the NR, RELAP and SVR groups. The thick short solid bar reflects the mean titer in each group for the pre and post-treatment sample. Statistical differences between pre- and post-therapy values were calculated using the nonparametric Wilcoxon signed rank test. The bottom of the figure shows the P value derived from summation of the antibody LU titers for the 3 antigens.