迟发型超敏反应（DTH）试验无反应性在抗逆转录病毒治疗期间不影响CD4重建或DTH反应的正常化。

Delayed-type hypersensitivity (DTH) test anergy does not impact CD4 reconstitution or normalization of DTH responses during antiretroviral therapy.

作者信息

Minidis Natascha M, Mesner Octavio, Agan Brian K, Okulicz Jason F

机构信息

Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; Infectious Disease Service, San Antonio Military Medical Center San Antonio, TX, USA.

Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

出版信息

J Int AIDS Soc. 2014 Feb 4;17(1):18799. doi: 10.7448/IAS.17.1.18799. eCollection 2014.

DOI:10.7448/IAS.17.1.18799

PMID:24499779

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3916671/

Abstract

INTRODUCTION

Delayed-type hypersensitivity (DTH) testing is an in vivo assessment of cell-mediated immunity. Although highly active antiretroviral therapy (HAART) improves immunologic parameters, the relationship between DTH responsiveness and CD4 gains on HAART is not completely understood. We investigated CD4 reconstitution and the change in DTH responses from treatment baseline through 24 months of viral load (VL)-suppressive HAART in the U.S. Military HIV Natural History Study.

METHODS

Treatment-naïve subjects with VL <400 copies/mL after ≥24 months on HAART were included (n=302). DTH testing consisted of ≥3 recall antigens, and responses were classified by the number of positive skin tests: anergic (0-1) or non-anergic (≥2). Pre-HAART DTH results were compared for the outcome of CD4 reconstitution at 24 months of HAART. Improvement in DTH responses was also analyzed for those anergic before HAART initiation.

RESULTS

Non-anergic responses were observed in 216 (72%) participants, while 86 (28%) individuals were anergic prior to HAART initiation. Demographically there were similar distributions of age at HIV diagnosis and HAART initiation, as well as gender and race or ethnicity. There were no significant differences between non-anergic and anergic participants in pre-HAART CD4 count (409 cells/μL, interquartile range (IQR) 315-517 vs. 373 cells/μL, IQR 228-487; p=0.104) and VL (4.3 log10 copies/mL, IQR 3.4-4.9 vs. 4.4 log10 copies/mL, IQR 3.6-5.0; p=0.292). Median CD4 gains 24 months after HAART initiation were similar between the non-anergic (220 cells/μL, IQR 115-358) and anergic groups (246 cells/μL, IQR 136-358; p=0.498). For individuals anergic before HAART initiation, DTH normalization occurred at 24 months post-HAART in the majority of participants (51 of 86, 59%). Normalization of DTH responses was not associated with CD4 count at HAART initiation (OR 0.73, 95% CI 0.47, 1.09 per 100 cells; p=0.129) nor with AIDS diagnoses prior to HAART (OR 0.34, 95% CI 0.04, 2.51; p=0.283).

CONCLUSIONS

DTH responsiveness has been shown to predict HIV disease progression independent of CD4 count in untreated individuals. In the setting of HAART, pre-HAART anergy does not appear to impact CD4 gains or the ability to normalize DTH responses after 24 months of VL-suppressive HAART.

摘要

引言

迟发型超敏反应（DTH）检测是对细胞介导免疫的一种体内评估。尽管高效抗逆转录病毒疗法（HAART）可改善免疫参数，但DTH反应性与HAART治疗中CD4细胞增加之间的关系尚未完全明确。在美国军事HIV自然史研究中，我们调查了从治疗基线到24个月病毒载量（VL）抑制性HAART治疗期间的CD4细胞重建情况以及DTH反应的变化。

方法

纳入在HAART治疗≥24个月后病毒载量<400拷贝/mL且未接受过治疗的受试者（n = 302）。DTH检测包括≥3种回忆抗原，反应根据阳性皮肤试验的数量分类：无反应性（0 - 1个）或有反应性（≥2个）。比较HAART治疗前DTH结果与HAART治疗24个月时CD4细胞重建的结果。还对HAART治疗开始前无反应性的受试者的DTH反应改善情况进行了分析。

结果

216名（72%）参与者观察到有反应性，而86名（28%）个体在HAART治疗开始前无反应性。在人口统计学方面，HIV诊断时和HAART治疗开始时的年龄分布、性别以及种族或族裔分布相似。HAART治疗前，有反应性和无反应性参与者的CD4细胞计数（409个细胞/μL，四分位间距（IQR）315 - 517 vs. 373个细胞/μL，IQR 228 - 487；p = 0.104）和病毒载量（4.3 log10拷贝/mL，IQR 3.4 - 4.9 vs. 4.4 log10拷贝/mL，IQR 3.6 - 5.0；p = 0.292）无显著差异。HAART治疗开始24个月后，有反应性组（220个细胞/μL，IQR 115 - 358）和无反应性组（246个细胞/μL，IQR 136 - 358；p = 0.498）的CD4细胞增加中位数相似。对于HAART治疗开始前无反应性的个体，大多数参与者（86名中的51名，59%）在HAART治疗后24个月时DTH反应恢复正常。DTH反应恢复正常与HAART治疗开始时的CD4细胞计数（每100个细胞的OR 0.73，95% CI 0.47，1.09；p = 0.129）以及HAART治疗前的艾滋病诊断均无关（OR 0.34，95% CI 0.04，2.51；p = 0.283）。