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抗逆转录病毒治疗期间病毒血症水平较低的HIV阳性成人的病毒学失败和全因死亡率

Virological failure and all-cause mortality in HIV-positive adults with low-level viremia during antiretroviral treatment.

作者信息

Elvstam Olof, Medstrand Patrik, Yilmaz Aylin, Isberg Per-Erik, Gisslén Magnus, Björkman Per

机构信息

Department of Translational Medicine, Clinical Infection Medicine Unit, Lund University, Malmö, Sweden.

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

出版信息

PLoS One. 2017 Jul 6;12(7):e0180761. doi: 10.1371/journal.pone.0180761. eCollection 2017.

Abstract

OBJECTIVE

Although most HIV-infected individuals achieve undetectable viremia during antiretroviral therapy (ART), a subset have low-level viremia (LLV) of varying duration and magnitude. The impact of LLV on treatment outcomes is unclear. We investigated the association between LLV and virological failure and/or all-cause mortality among Swedish patients receiving ART.

METHODS

HIV-infected patients from two Swedish HIV centers were identified from the nationwide register InfCare HIV. Subjects aged ≥15 years with triple agent ART were included at 12 months after treatment initiation if ≥2 following viral load measurements were available. Patients with 2 consecutive HIV RNA values ≥1000 copies/mL at this time point were excluded. Participants were stratified into four categories depending on viremia profiles: permanently suppressed viremia (<50 copies/mL), LLV 50-199 copies/mL, LLV 200-999 copies/mL and viremia ≥1000 copies/mL. Association between all four viremia categories and all-cause death was calculated using survival analysis with viremia as a time-varying covariate, so that patients could change viremia category during follow-up. Association between the three lower categories and virological failure (≥2 consecutive measurements ≥1000 copies/mL) was calculated in a similar manner.

RESULTS

LLV 50-199 copies/mL was recorded in 70/1015 patients (6.9%) and LLV 200-999 copies/mL in 89 (8.8%) during 7812 person-years of follow-up (median 6.5 years). LLV 200-999 copies/mL was associated with virological failure (adjusted hazard ratio 3.14 [95% confidence interval 1.41-7.03, p<0.01]), whereas LLV 50-199 copies/mL was not (1.01 [0.34-4.31, p = 0.99]; median follow-up 4.5 years). LLV 200-999 copies/mL had an adjusted mortality hazard ratio of 2.29 (0.98-5.32, p = 0.05) and LLV 50-199 copies/mL of 2.19 (0.90-5.37, p = 0.09).

CONCLUSIONS

In this Swedish cohort followed during ART for a median of 4.5 years, LLV 200-999 copies/mL was independently associated with virological failure. Patients with LLV had higher rates of all-cause mortality, although not statistically significant in multivariate analysis.

摘要

目的

尽管大多数感染HIV的个体在抗逆转录病毒治疗(ART)期间实现了病毒血症检测不到,但仍有一部分人存在持续时间和程度各异的低水平病毒血症(LLV)。LLV对治疗结果的影响尚不清楚。我们调查了瑞典接受ART治疗的患者中LLV与病毒学失败和/或全因死亡率之间的关联。

方法

从全国性登记处InfCare HIV中识别出两个瑞典HIV中心的HIV感染患者。年龄≥15岁且接受三联药物ART治疗的受试者在治疗开始12个月后纳入研究,前提是有≥2次病毒载量测量结果。此时连续2次HIV RNA值≥1000拷贝/mL的患者被排除。参与者根据病毒血症情况分为四类:病毒血症永久抑制(<50拷贝/mL)、LLV 50 - 199拷贝/mL、LLV 200 - 999拷贝/mL和病毒血症≥1000拷贝/mL。使用生存分析计算所有四类病毒血症与全因死亡之间的关联,将病毒血症作为随时间变化的协变量,以便患者在随访期间可能改变病毒血症类别。以类似方式计算三个较低类别与病毒学失败(≥2次连续测量≥1000拷贝/mL)之间的关联。

结果

在7812人年的随访期间(中位时间6.5年),1015例患者中有70例(6.9%)记录为LLV 50 - 199拷贝/mL,89例(8.8%)记录为LLV 200 - 999拷贝/mL。LLV 200 - 999拷贝/mL与病毒学失败相关(调整后的风险比为3.14 [95%置信区间1.41 - 7.03,p<0.01]),而LLV 50 - 199拷贝/mL则无关联(1.01 [0.34 - 4.31,p = 0.99];中位随访时间4.5年)。LLV 200 - 999拷贝/mL的调整后死亡风险比为2.29(0.98 - 5.32,p = 0.05),LLV 50 - 199拷贝/mL为2.19(0.90 - 5.37,p = 0.09)。

结论

在这个瑞典队列中,ART治疗期间的中位随访时间为4.5年,LLV 200 - 999拷贝/mL与病毒学失败独立相关。LLV患者的全因死亡率较高,尽管在多变量分析中无统计学意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/900c/5500364/b72bc323ad2f/pone.0180761.g001.jpg

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