Sustained Long-Term Decline in Anti-HCV Neutralizing Antibodies in HIV/HCV-Coinfected Patients Five Years after HCV Therapy: A Retrospective Study

Abstract

Background: This study evaluated titers and amplitudes of anti-E2 antibodies (anti-E2-Abs) and neutralizing antibodies against hepatitis C virus (HCV; anti-HCV-nAbs) in HIV/HCV-coinfected individuals over five years after successful HCV treatment completion. Methods: We retrospectively analyzed 76 HIV/HCV-coinfected patients achieving sustained virologic response post-HCV treatment. Plasma levels of anti-E2-Abs and anti-HCV-nAbs against five HCV genotypes (Gt1a, Gt1b, Gt2a, Gt3a, and Gt4a) were determined using ELISA and microneutralization assays, respectively. Statistical analyses comparing the three follow-up time points (baseline, one year, and five years post-HCV treatment) were performed using generalized linear mixed models, adjusting p-values with the false discovery rate (q-value). Results: Compared to baseline, anti-E2-Abs titers decreased at one year (1.9- to 2.3-fold, q-value < 0.001) and five years (3.4- to 9.1-fold, q-value < 0.001) post-HCV treatment. Anti-HCV-nAbs decreased 2.9- to 8.4-fold (q-value < 0.002) at one year and 17.8- to 90.4-fold (q-value < 0.001) at five years post-HCV treatment. Anti-HCV-nAbs titers against Gt3a were consistently the lowest. Nonresponse rates for anti-E2-Abs remained low throughout the follow-up, while anti-HCV-nAbs nonresponse rates increased 1.8- to 13.5-fold (q-value < 0.05) at five years post-HCV treatment, with Gt3a showing the highest nonresponse rate. Conclusions: Humoral immune responses against HCV decreased consistently one and five years post-HCV treatment, regardless of HCV genotype and previous HCV therapy or type of treatment (IFN- or DAA-based therapy). This decline was more pronounced for anti-HCV-nAbs, particularly against Gt3.

Keywords: HIV; HIV/HCV coinfection; anti-HCV therapy; broad-spectrum neutralizing antibodies; hepatitis C; sustained virologic response.

Figure 1

Anti-E2 antibodies ((A), anti-E2-Abs) and neutralizing antibodies against HCV ((B), anti-HCV-nAbs) titers during follow-up across HCV genotypes. Statistics: The data include individual values from each patient and the corresponding medians. Significant differences were determined using GLMM with gamma distribution and link (log). p-values were adjusted by the FDR (q-value). Abbreviations: AUC = area under the curve (arbitrary units); FDR = false discovery rate; GLMM = generalized linear mixed model; Gt = HCV genotype; HCV = hepatitis C virus; Yr = year.

Figure 2

Nonresponse rate of anti-E2 antibodies ((A), anti-E2-Abs) and neutralizing antibodies against HCV ((B), anti-HCV-nAbs) during follow-up across HCV genotypes. Statistics: Significant differences were determined using GLMM with binomial distribution and link (logit). p-values were adjusted by the FDR (q-value). Abbreviations: FDR = false discovery rate; GLMM = generalized linear mixed model; Gt = HCV genotype; HCV = hepatitis C virus.