Lin Weiyin, Li Liya, Guo Pengle, He Yaozu, He Haolan, Li Hong, Zhong Huolin, Liu Cong, Du Peishan, Cai Weiping, Tang Xiaoping, Li Linghua
Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China.
Front Med (Lausanne). 2023 Jun 13;10:1170208. doi: 10.3389/fmed.2023.1170208. eCollection 2023.
It is necessary to identify simple biomarkers that can efficiently predict the efficacy of long-term antiretroviral therapy (ART) against human immunodeficiency virus (HIV), especially in underdeveloped countries. We characterized the dynamic changes in plasma interleukin-18 (IL-18) and assessed its performance as a predictor of long-term virological response.
This was a retrospective cohort study of HIV-1-infected patients enrolled in a randomized controlled trial with a follow-up of 144 weeks of ART. Enzyme-linked immunosorbent assay was performed to evaluate plasma IL-18. Long-term virological response was defined as HIV-1 RNA <20 copies/mL at week 144.
Among the 173 enrolled patients, the long-term virological response rate was 93.1%. Patients with a long-term virological response had significantly lower levels of week 24 IL-18 than non-responders. We defined 64 pg./mL, with a maximum sum of sensitivity and specificity, as the optimal cutoff value of week 24 IL-18 level to predict long-term virological response. After adjusting for age, gender, baseline CD4+ T-cell count, baseline CD4/CD8 ratio, baseline HIV-1 RNA level, HIV-1 genotype and treatment strategy, we found that lower week 24 IL-18 level (≤64 vs. >64 pg./mL, a OR 19.10, 95% CI: 2.36-154.80) was the only independent predictor of long-term virological response.
Early on-treatment plasma IL-18 could act as a promising indicator for long-term virological response in patients with HIV-1 infection. Chronic immune activation and inflammation may represent a potential mechanism; further validation is necessary.
有必要确定能够有效预测长期抗逆转录病毒疗法（ART）治疗人类免疫缺陷病毒（HIV）疗效的简单生物标志物，尤其是在欠发达国家。我们对血浆白细胞介素-18（IL-18）的动态变化进行了特征分析，并评估了其作为长期病毒学应答预测指标的性能。
这是一项对参与随机对照试验的HIV-1感染患者进行的回顾性队列研究，ART随访144周。采用酶联免疫吸附测定法评估血浆IL-18。长期病毒学应答定义为第144周时HIV-1 RNA<20拷贝/毫升。
在173例入组患者中，长期病毒学应答率为93.1%。长期病毒学应答患者第24周的IL-18水平显著低于无应答者。我们将64 pg./mL定义为预测长期病毒学应答的第24周IL-18水平的最佳临界值，此时敏感性和特异性之和最大。在调整年龄、性别、基线CD4+T细胞计数、基线CD4/CD8比值、基线HIV-1 RNA水平、HIV-1基因型和治疗策略后，我们发现较低的第24周IL-18水平（≤64 vs.>64 pg./mL，优势比19.10，95%%%95%CI：2.36-154.80）是长期病毒学应答的唯一独立预测指标。
治疗早期血浆IL-18可作为HIV-1感染患者长期病毒学应答的一个有前景的指标。慢性免疫激活和炎症可能是一种潜在机制；需要进一步验证。
