Background

Complete recovery of the CD4 T cell count is uncommon among chronically HIV-infected individuals with very low pre-treatment CD4 count. We studied the prevalence of chronically immune recovery and its associated factors including immune characteristics chronic HIV-infected Thais.

Methods

Treatment-naïve participants (n ​= ​375) from the HIV-NAT 006 cohort with a pre-treatment CD4 T cell count after initiating antiretroviral therapy (ART) and having achieved a suppressed viremia (HIV-RNA level ​< ​400 copies/mL) were retrospectively followed at the Thai Red Cross AIDS Research Centre, Bangkok, Thailand. Suboptimal immune recovery (SIR) was defined as having a CD4⁺ T cell count <200 ​cells/mm³ for 3 years after ART initiation. A case-control sub-study matched for age, sex and pre-ART CD4 T cell count was conducted to compare immunological characteristics between SIR (n ​= ​17) and non-SIR (n ​= ​24) participants. Immunological biomarkers such as interleukin-7 (IL-7) and soluble CD14 (sCD14) and other covariates including cytomegalovirus (CMV) DNA level, baseline hemoglobin level, hepatitis B and C co-infections, and T cell subsets associated with immune activation and exhaustion were evaluated.

Results

Among 375 participants with pre-ART CD4 T cell counts < 200 ​cells/mm³, the prevalence of SIR was 39.7%, 19.7% and 7.7% at years 1, 2 and 3 after starting ART, respectively. In a multivariate analysis, a pre-ART CD4 T cell count ≤100 ​cells/mm³ (adjusted odds ratio [aOR] 9.45, 95% CI 2.92–30.61, p ​< ​0.001), older age (aOR 1.07, 95% CI 1.01–1.13, p ​= ​0.029) and baseline HIV-RNA level (aOR 0.36, 95% CI 0.21–0.59, p ​< ​0.001) were independently associated with SIR at year 3 after ART initiation. In the matched case-control sub-study (cases ​= ​17, controls ​= ​24), there was a higher prevalence of hepatitis C co-infection (18.8% vs. 0%, p ​= ​0.05), lower sCD14 levels (mean, 6.23 vs. 6.27 log₁₀ ​pg/mL, p ​= ​0.04), lower CD8 T cell counts (mean, 514 vs. 876, p ​= ​0.0003), lower CD4/CD8 T cell ratio (mean, 0.27 vs. 0.41, p ​= ​0.01) and higher expression of PD1 on CD8⁺ T cells (74.2% vs. 65.1%, p ​= ​0.02) observed in SIR participants compared to their non-SIR counterparts at year 3 after ART initiation.

Conclusions

Nearly 10% of the study participants who had achieved virological suppression failed to recover a CD4 T cell count > 200 cells/mm³ after 3 years of ART which was with a very low pre-ART CD4 T cell count and older age. The long-term clinical outcomes of SIR participants need to be further explored.

中文翻译：

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泰国治疗前 CD4 T 细胞计数 <200 细胞/mm3 的 HIV 感染者开始抗逆转录病毒治疗后免疫反应欠佳的特征

背景

在治疗前 CD4 计数非常低的慢性 HIV 感染者中，CD4 T 细胞计数完全恢复并不常见。我们研究了慢性免疫恢复的患病率及其相关因素，包括慢性 HIV 感染的泰国人的免疫特征。

方法

来自 HIV-NAT 006 队列的初治参与者 (n = 375)，在开始抗逆转录病毒治疗 (ART) 并达到抑制病毒血症 (HIV-RNA 水平 <400 拷贝) 后具有治疗前 CD4 T 细胞计数/mL）在泰国曼谷的泰国红十字会艾滋病研究中心进行了回顾性随访。次优免疫恢复 (SIR) 定义为 CD4 ⁺ T 细胞计数 <200 细胞/mm ³ART 开始后 3 年。进行了一项与年龄、性别和 ART 前 CD4 T 细胞计数相匹配的病例对照子研究，以比较 SIR（n = 17）和非 SIR（n = 24）参与者之间的免疫学特征。免疫生物标志物，例如白细胞介素 7 (IL-7) 和可溶性 CD14 (sCD14) 以及其他协变量，包括巨细胞病毒 (CMV) DNA 水平、基线血红蛋白水平、乙型和丙型肝炎合并感染，以及与免疫激活和免疫相关的 T 细胞亚群疲劳进行了评估。

结果

在 ART 前 CD4 T 细胞计数 < 200 个/mm ³的 375 名参与者中，在开始 ART 后的第 1 年、第 2 年和第 3 年，SIR 的患病率分别为 39.7%、19.7% 和 7.7%。在多变量分析中，ART 前 CD4 T 细胞计数≤100 细胞/mm ³（调整优势比 [aOR] 9.45, 95% CI 2.92–30.61, p <<0.001），年龄较大（aOR 1.07, 95 % CI 1.01–1.13，p = ​0.029）和基线 HIV-RNA 水平（aOR 0.36，95% CI 0.21–0.59，p​<0.001）与 ART 开始后第 3 年的 SIR 独立相关。在匹配的病例对照子研究中（病例 = ​17，对照 = ​24），丙型肝炎合并感染的患病率较高（18.8% vs. 0%，p = 0.05），较低sCD14 水平（平均 6.23 对 6.27 log ₁₀ ​pg/mL，p​=​0.04），较低的 CD8 T 细胞计数（平均值，514 与 876，p​=​0.0003），较低的 CD4/CD8 T 细胞比率（平均值，0.27 与 0.41，p​= ​0.01）和更高的 PD1 在 CD8 ⁺ T 细胞上的表达（74.2% 对 65.1%，p = 0.02）在 ART 开始后的第 3 年与非 SIR 参与者相比，SIR 参与者观察到。

结论

近 10% 实现病毒学抑制的研究参与者在 ART 3 年后未能恢复 CD4 T 细胞计数 > 200 个细胞/mm ³，这是 ART 前 CD4 T 细胞计数非常低且年龄较大的情况。SIR参与者的长期临床结果需要进一步探索。