Department of Translational Medicine, Lund University, Malmö, Sweden.
Department of Infectious Diseases, Växjö Central Hospital, Växjö, Sweden.
Clin Infect Dis. 2023 Jan 6;76(1):25-31. doi: 10.1093/cid/ciac762.
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.
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.
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.
Both blips and LLV during ART are associated with increased risk of subsequent VF.
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。
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。
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。
ART 期间的 VL 一过性升高和 LLV 均与随后 VF 的风险增加相关。