与 HIV/AIDS 患者延迟接受治疗相关的临床参数、选定的 HLA 和趋化因子基因变异。

Clinical parameters, selected HLA and chemokine gene variants associated with late presentation into care of people living with HIV/AIDS.

机构信息

Department of Infectious, Tropical Diseases and Immune Deficiency, Pomeranian Medical University in Szczecin, Szczecin, Poland.

出版信息

Infect Genet Evol. 2022 Jan;97:105180. doi: 10.1016/j.meegid.2021.105180. Epub 2021 Dec 9.

DOI:10.1016/j.meegid.2021.105180

PMID:34896288

Abstract

INTRODUCTION

Late presentation into care remains a significant problem in the diagnosis of HIV infection, and may negatively impact the Joint United Nations Program HIV/AIDS elimination targets. Host genetics affects the tempo of HIV disease progression and therefore may influence clinical status at care entry.

MATERIALS AND METHODS

Longitudinal data were collected for 863 Caucasian patients followed up at Pomeranian Medical University, Szczecin, Poland. Single nucleotide polymorphisms in CCR2 (rs1799864), CX3CR1 (rs3732378), HLAC-35 (rs9264942), CCR5 promoter (rs1799988) as well as 32 base pair CCR5 mutation and HLA-B*5701 genotypes were correlated with the clinical and immunologic patient status at care entry. Late presentation was defined as baseline CD4 lymphocyte count <350 cells/μL or history of AIDS-defining illness, while advanced HIV disease as baseline CD4 lymphocyte count <200 cells/μL or AIDS.

RESULTS

Of the analyzed gene variants, the CCR2 (rs1799864) GG genotype was more frequent among patients presenting for care with a CD4 lymphocyte count <200/μL (82.6% for GG homozygotes vs. 74.5% for allele A carriers, p = 0.01). The presence of the heterozygous wt/Δ32 genotype at the CCR5 gene was associated with a higher frequency of asymptomatic infection (18.9% for wt/Δ32 heterozygotes vs. 12% for wt/wt homozygotes, p = 0.03). As expected, this association was also observed among late presenters compared to patients presenting for care earlier (13.7% vs. 19,7%, respectively, p = 0.04). Finally, HLA-B*5701 was less common among late presenters (5%) compared to patients who entered care early (9.6%, p = 0.01) or patients with advanced HIV disease (8.9% vs. 5.2%, p = 0.02).

CONCLUSIONS

Late presentation was associated with the GG homozygous genotype at the CCR2 rs1799864 SNP, while both the HLA-B*5701 variant and the CCR5 wt/Δ32 were associated with more favorable clinical profile at care entry.

摘要

简介

在 HIV 感染的诊断中，晚期就诊仍然是一个严重的问题，可能会对联合国艾滋病规划署联合消除目标产生负面影响。宿主遗传学影响 HIV 疾病进展的速度，因此可能会影响就诊时的临床状况。

材料与方法

对在波兰什切青波美拉尼亚医科大学接受随访的 863 名白种人患者进行了纵向数据收集。将 CCR2（rs1799864）、CX3CR1（rs3732378）、HLAC-35（rs9264942）、CCR5 启动子（rs1799988）中的单核苷酸多态性以及 32 碱基对 CCR5 突变和 HLA-B*5701 基因型与就诊时的临床和免疫患者状况相关联。晚期就诊被定义为基线 CD4 淋巴细胞计数<350 个/μL 或艾滋病定义性疾病史，而晚期 HIV 疾病则定义为基线 CD4 淋巴细胞计数<200 个/μL 或艾滋病。

结果

在所分析的基因变异中，CCR2（rs1799864）GG 基因型在就诊时 CD4 淋巴细胞计数<200/μL 的患者中更为常见（GG 纯合子为 82.6%，而等位基因 A 携带者为 74.5%，p=0.01）。在 CCR5 基因中存在杂合 wt/Δ32 基因型与无症状感染的频率较高相关（wt/Δ32 杂合子为 18.9%，wt/wt 纯合子为 12%，p=0.03）。如预期的那样，这种关联在晚期就诊者中也观察到，与早期就诊者相比（分别为 13.7%和 19.7%，p=0.04）。最后，与早期就诊者或晚期 HIV 疾病患者相比，HLA-B*5701 在晚期就诊者中较为罕见（分别为 5%、8.9%和 5.2%，p=0.01）。