Sachithanandham Jaiprasath, Leep-Lazar Julia, Quinn Jeffrey, Bowden Kenneth, Balasubramaniam Prasanthy, Ward Kathleen, Ribeiro Ruy M, Sulkowski Mark S, Balagopal Ashwin
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University School of Public Health, Baltimore, Maryland.
Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.
J Infect Dis. 2025 Jun 2;231(5):1299-1308. doi: 10.1093/infdis/jiae598.
Hepatitis C virus (HCV) infects nearly one-fourth of people with human immunodeficiency virus (HIV). The role of direct-acting antivirals (DAAs) on immune activation in people with HIV (PWH) and HCV is poorly understood.
We quantified plasma HCV RNA and CXCL10 in persons with HCV monoinfection versus HIV/HCV coinfection receiving sofosbuvir-velpatasvir. Single-cell laser capture microdissection was applied to liver biopsies obtained before and within 4-7 days of DAA initiation to estimate HCV clearance and changes in interferon-stimulated genes (ISGs).
We enrolled 10 people with chronic genotype 1a HCV: 5 were PWH with ART-suppressed viremia and CD4+ T cell counts >200 cells/µL. First- and second-phase plasma HCV RNA kinetics were not different between groups. Median (min-max) proportions of infected hepatocytes at biopsy 1 were 0.06 (0.01-0.59) in HCV monoinfection and 0.21 (0.04-0.87) in HIV/HCV coinfection and did not differ. Participants had lower intracellular HCV RNA levels at biopsy 2. CXCL10 levels declined in both groups but were higher in coinfection than in monoinfection even at the end of treatment. The proportion of cells expressing ISGs diminished in monoinfection but increased in coinfection.
Whereas DAAs rapidly cleared intrahepatic HCV in both groups, immune activation was slower to diminish in PWH. Residual immune activation in PWH warrants further exploration. Clinical Trials Registration. NCT02938013.
丙型肝炎病毒（HCV）感染了近四分之一的人类免疫缺陷病毒（HIV）感染者。直接抗病毒药物（DAAs）对HIV感染者（PWH）和HCV感染者免疫激活的作用尚不清楚。
我们对接受索磷布韦-维帕他韦治疗的HCV单一感染与HIV/HCV合并感染患者的血浆HCV RNA和CXCL10进行了定量。应用单细胞激光捕获显微切割技术对DAA开始治疗前及开始治疗后4 - 7天内获取的肝活检组织进行分析，以评估HCV清除情况及干扰素刺激基因（ISGs）的变化。
我们招募了10例慢性1a基因型HCV感染者：5例为PWH，其病毒血症得到抗逆转录病毒治疗（ART）抑制，CD4 + T细胞计数>200个/μL。两组间第一阶段和第二阶段血浆HCV RNA动力学无差异。活检1时感染肝细胞的中位数（最小值 - 最大值）比例在HCV单一感染组为0.06（0.01 - 0.59），在HIV/HCV合并感染组为0.21（0.04 - 0.87），两者无差异。参与者在活检2时细胞内HCV RNA水平较低。两组CXCL10水平均下降，但即使在治疗结束时，合并感染组的CXCL10水平仍高于单一感染组。单一感染组中表达ISGs的细胞比例减少，而合并感染组中则增加。
虽然DAAs在两组中均迅速清除肝内HCV，但PWH的免疫激活减弱较慢。PWH中残留的免疫激活值得进一步探索。临床试验注册编号：NCT02938013。
