Sepúlveda-Crespo Daniel, Volpi Camilla, Amigot-Sánchez Rafael, Yélamos María Belén, Díez Cristina, Gómez Julián, Hontañón Víctor, Berenguer Juan, González-García Juan, Martín-Escolano Rubén, Resino Salvador, Martínez Isidoro
Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo, Km 2.2, 28220 Majadahonda (Madrid), Spain.
Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain.
Pharmaceuticals (Basel). 2024 Aug 30;17(9):1152. doi: 10.3390/ph17091152.
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. 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 -values with the false discovery rate (-value). Compared to baseline, anti-E2-Abs titers decreased at one year (1.9- to 2.3-fold, -value < 0.001) and five years (3.4- to 9.1-fold, -value < 0.001) post-HCV treatment. Anti-HCV-nAbs decreased 2.9- to 8.4-fold (-value < 0.002) at one year and 17.8- to 90.4-fold (-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 (-value < 0.05) at five years post-HCV treatment, with Gt3a showing the highest nonresponse rate. 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.
本研究评估了丙型肝炎病毒（HCV）成功治愈五年后的HIV/HCV合并感染个体中抗E2抗体（抗E2-Abs）的滴度和幅度以及抗HCV中和抗体（抗HCV-nAbs）。我们回顾性分析了76例HCV治疗后获得持续病毒学应答的HIV/HCV合并感染患者。分别使用酶联免疫吸附测定（ELISA）和微量中和试验测定针对五种HCV基因型（Gt1a、Gt1b、Gt2a、Gt3a和Gt4a）的抗E2-Abs和抗HCV-nAbs的血浆水平。使用广义线性混合模型对三个随访时间点（基线、HCV治疗后一年和五年）进行统计分析，并使用错误发现率调整P值（P值）。与基线相比，HCV治疗后一年抗E2-Abs滴度下降（1.9至2.3倍，P值<0.001），五年后下降（3.4至9.1倍，P值<0.001）。HCV治疗后一年抗HCV-nAbs下降2.9至8.4倍（P值<0.002），五年后下降17.8至90.4倍（P值<0.001）。针对Gt3a的抗HCV-nAbs滴度始终最低。在整个随访过程中，抗E2-Abs的无应答率一直较低，而HCV治疗后五年抗HCV-nAbs的无应答率增加了1.8至13.5倍（P值<0.05），其中Gt3a的无应答率最高。无论HCV基因型、先前的HCV治疗或治疗类型（基于干扰素或直接抗病毒药物的治疗）如何，HCV治疗后一年和五年针对HCV的体液免疫反应均持续下降。这种下降在抗HCV-nAbs中更为明显，尤其是针对Gt3。
