外周活化CD8+T细胞高比例持续存在可预测接受cART治疗的HIV阳性受试者的细胞学HPV相关发育异常。

Persistence of High Percentage of Peripheral Activated CD8+ T Cells Predict Cytologic HPV-Related Dysplasia in cART-Treated, HIV-Positive Subjects.

作者信息

Mondatore Debora, Bai Francesca, Augello Matteo, Giovenzana Marco, Pisani Ceretti Andrea, Bono Valeria, Opocher Enrico, d'Arminio Monforte Antonella, Marchetti Giulia Carla, Tincati Camilla

机构信息

Clinic of Infectious Diseases, Department of Health Sciences, ASST Santi Paolo e Carlo, University of Milan, Milan, Italy.

Hepato-biliopancreatic and Digestive Surgery, Department of Health Sciences, ASST Santi Paolo e Carlo, University of Milan, Milan, Italy.

出版信息

Open Forum Infect Dis. 2022 Jan 30;9(4):ofac046. doi: 10.1093/ofid/ofac046. eCollection 2022 Apr.

DOI:10.1093/ofid/ofac046

PMID:35291446

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8918388/

Abstract

BACKGROUND

People with HIV are at increased risk of human papillomavirus (HPV) disease progression, given the persistence of immune activation and residual inflammation despite effective combination antiretroviral therapy (cART). Whether a low CD4:CD8 T-cell ratio, known to mirror peripheral immune dysfunction, is associated with squamous intraepithelial lesions (SILs) is unknown.

METHODS

This was a retrospective cohort study on cART-treated HIV-positive subjects undergoing screening for HPV-related dysplasia (anal/cervical cytology and HPV genotyping). SIL was defined as the presence of either atypical squamous cells of undetermined significance (ASCUS), low-grade SILs, or high-grade SILs. Demographic and viro-immunological parameters (T-cell count, CD4:CD8 T-cell ratio, CD8+ CD38+ T-cell percentage) at the time of screening were analyzed by the chi-square test, Mann-Whitney test, and multivariate logistic regression analysis.

RESULTS

A total of 419 cART-treated subjects were included. Half of the patients had cervical/anal SIL. Individuals with SIL were more commonly males, were men who have sex with men, were coinfected with , had been treated with integrase inhibitor (INSTI)-based cART regimens, and had a shorter time since HIV diagnosis and cART initiation than subjects with normal cytology. CD38+ CD8+ T-cell percentage, but not the CD4:CD8 T-cell ratio, correlated with SILs. HPV infection, especially with multiple and high-risk genotypes, was confirmed to be associated with SIL. In multivariate analysis, the only factors independently associated with cervical/anal dysplasia were HPV infection and harboring higher percentages of peripheral activated CD38+ CD8+ T cells.

CONCLUSIONS

HPV infection is the major driver of dysplasia in the setting of HIV infection. In this study, CD8+ CD38+ T cells were an independent predictor of dysplasia in cART-treated subjects, while CD4:CD8 T-cell ratio was not. In the setting of HIV-HPV coinfection, CD4:CD8 T-cell ratio may not fully capture the alterations of HPV-specific immunity.

摘要

背景

尽管接受了有效的联合抗逆转录病毒疗法（cART），但由于免疫激活和残余炎症持续存在，HIV感染者患人乳头瘤病毒（HPV）疾病进展的风险增加。低CD4:CD8 T细胞比率反映外周免疫功能障碍，它是否与鳞状上皮内病变（SIL）相关尚不清楚。

方法

这是一项针对接受cART治疗的HIV阳性受试者的回顾性队列研究，这些受试者正在接受HPV相关发育异常筛查（肛门/宫颈细胞学检查和HPV基因分型）。SIL定义为存在意义不明确的非典型鳞状细胞（ASCUS）、低级别SIL或高级别SIL。筛查时的人口统计学和病毒免疫学参数（T细胞计数、CD4:CD8 T细胞比率、CD8 + CD38 + T细胞百分比）通过卡方检验、曼-惠特尼检验和多因素逻辑回归分析进行分析。

结果

共纳入419名接受cART治疗的受试者。一半的患者有宫颈/肛门SIL。患有SIL的个体更常见为男性、男男性行为者、合并感染、接受过基于整合酶抑制剂（INSTI）的cART方案治疗，并且自HIV诊断和开始cART以来的时间比细胞学正常的受试者短。CD38 + CD8 + T细胞百分比与SIL相关，而CD4:CD8 T细胞比率与SIL无关。HPV感染，尤其是多重和高危基因型感染，被证实与SIL相关。在多因素分析中，与宫颈/肛门发育异常独立相关的唯一因素是HPV感染和外周活化CD38 + CD8 + T细胞比例较高。