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高等级肛门上皮内瘤与 HIV-1 RNA 直肠脱落有关,而 HIV-1 RNA 直肠脱落与接受抗病毒治疗的 HIV 感染者 HIV-1 RNA 检测不到有关。

High-grade anal intraepithelial neoplasia is associated with HIV-1 RNA rectal shedding in virologically suppressed MSM.

机构信息

Infectious Diseases Unit, Hospital General de Elche & Universidad Miguel Hernández.

Statistics, Operative Research Center, Universidad Miguel Hernández.

出版信息

AIDS. 2018 May 15;32(8):1017-1024. doi: 10.1097/QAD.0000000000001794.

Abstract

OBJECTIVE

The protective effect of ART has not yet been definitively established in MSM. We aimed to characterize the factors associated with persistent HIV-1 RNA rectal shedding.

METHODS

Prospective study including virologically suppressed MSM from an HIV cohort. High-resolution anoscopy (HRA) was performed for screening of anal dysplasia, and rectal sampling for HIV-1 RNA quantification and sexually transmitted infections (STIs) investigation through multiplex PCR. Both generalized linear mixed (GLM) and zero-altered negative binomial (ZANB) models were performed.

RESULTS

One hundred and fifty-five rectal swab samples from 132 virologically suppressed MSM were included. HIV-1 RNA was detectable in 61 (39.3%) samples, with median (IQR) rectal viral load (rVL) of 295.8 (158.8-522) copies/swab. Multivariable GLM showed that the presence of high-grade anal intraepithelial neoplasia (HG-AIN; OR 2.85 [95% CI 1.10-7.38]) and a protease inhibitor-based regimen (OR 2.49 [0.98-6.34]) resulted in increased risk for rectal HIV-1 shedding, whereas higher nadir CD4+/CD8+ T-cell ratio (OR 0.18 [0.04-0.93]) was negatively associated with rectal shedding. ZANB analyses showed that the best predictors of having detectable rVL were lower nadir CD4+/CD8+ T-cell ratio (OR 0.98 [0.96-0.99]) and PI-based regimens (OR 4.85 [1.29-18.24]); the presence of HG-AIN (RR 2.50 [1.41-4.45]), and a higher burden of STIs (RR 1.39 [1.03-1.85]) were predictors of rectal HIV-1 shedding intensity.

CONCLUSION

The prevalence of HIV-1 RNA rectal shedding is high in virologically suppressed MSM. In addition to ART and the immune system integrity, local factors, including the co-existence of HG-AIN and the burden of STIs, may account for the persistence of HIV-1 RNA shedding in rectal mucosa.

摘要

目的

抗逆转录病毒疗法(ART)对男男性行为者(MSM)的保护作用尚未得到明确证实。本研究旨在确定与持续性 HIV-1 RNA 直肠脱落相关的因素。

方法

本前瞻性研究纳入了 HIV 队列中病毒学抑制的 MSM 患者。对其进行高分辨率肛门镜检查(HRA)以筛查肛门发育不良,并进行直肠取样以通过多重聚合酶链反应(PCR)进行 HIV-1 RNA 定量和性传播感染(STI)检测。本研究同时采用广义线性混合(GLM)和零调整负二项式(ZANB)模型。

结果

本研究纳入了 132 例病毒学抑制的 MSM 的 155 份直肠拭子样本。61 份(39.3%)样本可检测到 HIV-1 RNA,直肠病毒载量(rVL)中位数(IQR)为 295.8(158.8-522)拷贝/拭子。多变量 GLM 显示,高级别肛门上皮内瘤变(HG-AIN;比值比 [OR] 2.85[95%CI 1.10-7.38])和基于蛋白酶抑制剂的治疗方案(OR 2.49[0.98-6.34])与直肠 HIV-1 脱落风险增加相关,而较低的 CD4+/CD8+T 细胞比值最低点(OR 0.18[0.04-0.93])与直肠脱落呈负相关。ZANB 分析显示,可检测到 rVL 的最佳预测因子为较低的 CD4+/CD8+T 细胞比值最低点(OR 0.98[0.96-0.99])和基于蛋白酶抑制剂的治疗方案(OR 4.85[1.29-18.24]);HG-AIN 的存在(RR 2.50[1.41-4.45])和 STI 负担较高(RR 1.39[1.03-1.85])是 HIV-1 RNA 直肠脱落强度的预测因子。

结论

病毒学抑制的 MSM 中 HIV-1 RNA 直肠脱落的发生率很高。除了 ART 和免疫系统完整性外,局部因素,包括 HG-AIN 的共存和 STI 负担,可能是 HIV-1 RNA 持续脱落于直肠黏膜的原因。

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