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抗逆转录病毒治疗期间低水平病毒血症和病毒学突破后的病毒学失败:来自欧洲多中心队列的结果。

Virologic Failure Following Low-level Viremia and Viral Blips During Antiretroviral Therapy: Results From a European Multicenter Cohort.

机构信息

Department of Translational Medicine, Lund University, Malmö, Sweden.

Department of Infectious Diseases, Växjö Central Hospital, Växjö, Sweden.

出版信息

Clin Infect Dis. 2023 Jan 6;76(1):25-31. doi: 10.1093/cid/ciac762.

Abstract

BACKGROUND

It is unclear whether low-level viremia (LLV), defined as repeatedly detectable viral load (VL) of <200 copies/mL, and/or transient viremic episodes (blips) during antiretroviral therapy (ART), predict future virologic failure. We investigated the association between LLV, blips, and virologic failure (VF) in a multicenter European cohort.

METHODS

People with HIV-1 who started ART in 2005 or later were identified from the EuResist Integrated Database. We analyzed the incidence of VF (≥200 copies/mL) depending on viremia exposure, starting 12 months after ART initiation (grouped as suppression [≤50 copies/mL], blips [isolated VL of 51-999 copies/mL], and LLV [repeated VLs of 51-199 copies/mL]) using Cox proportional hazard models adjusted for age, sex, injecting drug use, pre-ART VL, CD4 count, HIV-1 subtype, type of ART, and treatment experience. We queried the database for drug-resistance mutations (DRM) related to episodes of LLV and VF and compared those with baseline resistance data.

RESULTS

During 81 837 person-years of follow-up, we observed 1424 events of VF in 22 523 participants. Both blips (adjusted subhazard ratio [aHR], 1.7; 95% confidence interval [CI], 1.3-2.2) and LLV (aHR, 2.2; 95% CI, 1.6-3.0) were associated with VF, compared with virologic suppression. These associations remained statistically significant in subanalyses restricted to people with VL <200 copies/mL and those starting ART 2014 or later. Among people with LLV and genotype data available within 90 days following LLV, 49/140 (35%) had at least 1 DRM.

CONCLUSIONS

Both blips and LLV during ART are associated with increased risk of subsequent VF.

摘要

背景

目前尚不清楚低水平病毒血症(LLV),即反复检测到的病毒载量(VL)<200 拷贝/毫升,和/或抗病毒治疗(ART)期间的短暂病毒血症发作(VL 一过性升高),是否与未来的病毒学失败(VF)相关。我们在一个多中心的欧洲队列中研究了 LLV、VL 一过性升高与 VF 之间的关系。

方法

从 EuResist 综合数据库中确定了 2005 年或之后开始 ART 的 HIV-1 感染者。我们分析了 12 个月后(分组为抑制[≤50 拷贝/毫升]、VL 一过性升高[孤立的 VL 为 51-999 拷贝/毫升]和 LLV[重复的 VL 为 51-199 拷贝/毫升])根据病毒血症暴露情况发生 VF(≥200 拷贝/毫升)的发生率,使用 Cox 比例风险模型进行调整,包括年龄、性别、使用注射毒品、ART 前 VL、CD4 计数、HIV-1 亚型、ART 类型和治疗经验。我们在数据库中查询与 LLV 和 VF 相关的耐药突变(DRM),并将其与基线耐药数据进行比较。

结果

在 81837 人年的随访中,我们观察到 22523 名参与者中有 1424 例 VF 事件。VL 一过性升高(调整后的亚危险比[aHR],1.7;95%置信区间[CI],1.3-2.2)和 LLV(aHR,2.2;95%CI,1.6-3.0)与 VF 相关,与病毒学抑制相比。这些关联在限制为 VL<200 拷贝/毫升的人群和 2014 年或之后开始 ART 的人群的亚分析中仍然具有统计学意义。在有 LLV 和基因型数据且在 LLV 后 90 天内可用的人群中,49/140(35%)至少有 1 个 DRM。

结论

ART 期间的 VL 一过性升高和 LLV 均与随后 VF 的风险增加相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6edc/9825828/935fd0cff99c/ciac762f1.jpg

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