University of Maryland School of Medicine, Institute of Human Virology, Baltimore, Maryland, USA.
University of Maryland Medical Center, Midtown Campus, Baltimore, Maryland, USA.
HIV Med. 2024 May;25(5):622-627. doi: 10.1111/hiv.13612. Epub 2024 Jan 25.
Hepatitis C virus (HCV)/HIV co-infection has been identified as a risk for impaired CD4+ T-cell recovery, possibly mediated by HCV-induced liver fibrosis and/or immune activation. As HCV direct-acting antivirals (DAAs) may partially reverse liver fibrosis and immune activation, sustained HCV virological response (SVR) may lead to improved CD4 recovery. We explored the effect of HCV DAA-induced SVR on CD4 recovery among patients living with both HCV and HIV, including those with poor CD4 recovery on antiretroviral therapy (immunological non-responders [INRs]).
Subjects aged ≥18 years living with both HIV and HCV who achieved SVR with DAA were included. Pre-DAA CD4 counts were included only after sustained HIV viral suppression and HIV viral suppression was maintained for the duration of the study. Segmented regression of interrupted time series analysis was used to evaluate changes in median CD4 count in the pre-DAA period (-36 months) versus the post-DAA period (+36 months).
In total, 156 patients were included. In the full cohort, median CD4 counts increased by 15% (p = 0.002) in the 6-month period following DAA initiation, whereafter CD4 counts decreased by 2.7% per 6-month period (p = 0.004). Among the 13 INRs, there was no immediate effect on median CD4 in the first 6 months after DAA initiation, whereafter there was a sustained CD4 increase (4.1% per 6-month time interval [p = 0.02]). In total, 54% of INRs recorded a post-DAA CD4 count of >350 cells/mm.
Successful DAA therapy induced a modest immediate CD4 immunological reconstitution among this cohort of patients living with both HIV and HCV, although this effect waned with time. By contrast, among INRs, achieving HCV SVR led to slower but sustained CD4 count recovery.
丙型肝炎病毒（HCV）/人类免疫缺陷病毒（HIV）合并感染已被确定为 CD4+T 细胞恢复受损的风险因素，其可能由 HCV 诱导的肝纤维化和/或免疫激活介导。由于 HCV 直接作用抗病毒药物（DAA）可能部分逆转肝纤维化和免疫激活，持续的 HCV 病毒学应答（SVR）可能导致 CD4 恢复改善。我们探索了 HCV DAA 诱导的 SVR 对同时患有 HCV 和 HIV 的患者的 CD4 恢复的影响，包括那些在抗逆转录病毒治疗中 CD4 恢复不良的患者（免疫无应答者[INRs]）。
纳入年龄≥18 岁且经 DAA 治疗实现 SVR 的同时患有 HIV 和 HCV 的患者。仅在持续 HIV 病毒抑制后纳入 DAA 前的 CD4 计数，并且在研究期间维持 HIV 病毒抑制。采用中断时间序列分析的分段回归来评估 DAA 前（-36 个月）与 DAA 后（+36 个月）期间的中位数 CD4 计数的变化。
总共纳入了 156 名患者。在全队列中，DAA 起始后 6 个月内 CD4 计数中位数增加了 15%（p=0.002），此后每 6 个月 CD4 计数下降 2.7%（p=0.004）。在 13 名 INRs 中，DAA 起始后前 6 个月内中位数 CD4 计数没有立即变化，此后 CD4 计数持续增加（每 6 个月时间间隔增加 4.1%[p=0.02]）。总共，54%的 INRs 记录的 DAA 后 CD4 计数大于 350 个细胞/mm³。
成功的 DAA 治疗在本同时患有 HIV 和 HCV 的患者队列中诱导了适度的即刻 CD4 免疫重建，尽管这种效应随时间而减弱。相比之下，在 INRs 中，实现 HCV SVR 导致较慢但持续的 CD4 计数恢复。
