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柬埔寨抗逆转录病毒治疗十年经验:患者特征及治疗结果的趋势

Ten year experience with antiretroviral treatment in Cambodia: Trends in patient characteristics and treatment outcomes.

作者信息

Lay Phirum, An Sokkab, Soeung Sunpiseth, Srey Pich Sovannary, Thai Sopheak, Lynen Lutgarde, Griensven Johan van

机构信息

Sihanouk Hospital Center of HOPE, Phnom Penh, Cambodia.

Institute of Tropical Medicine, Antwerp, Belgium.

出版信息

PLoS One. 2017 Nov 14;12(11):e0185348. doi: 10.1371/journal.pone.0185348. eCollection 2017.

Abstract

BACKGROUND

Although HIV disease stage at ART initiation critically determines ART outcomes, few reports have longitudinally monitored this within Asia. Using prospectively collected data from a large ART program at Sihanouk Hospital Center of Hope in Cambodia, we report on the change in patient characteristics and outcomes over a ten-year period.

METHODS

We conducted a retrospective analysis including all adults (≥ 18 years old) starting ART from March 2003-March 2013 in a non-governmental hospital in Phnom Penh, Cambodia. The cumulative incidence of death, lost to follow-up (LTFU), attrition (death or LTFU) and first line treatment failure were calculated using Kaplan-Meier methods. Independent risk factors for these outcomes were determined using Cox regression modeling.

RESULTS

Over the ten-year period, 3581 patients initiated ART with a median follow-up time of 4.8 years (IQR 2.8-7.2). The median age was 35 years (IQR 30-41), 54% were female. The median CD4 count at ART initiation increased from 22 cells/μL (IQR 4-129) in 2003 to 218 (IQR 57-302) in 2013. Over the 10 year period, a total of 282 (7.9%) individuals died and 433 (12.1%) were defined LTFU. Program attrition (died or LTFU) was 11.1% (95% CI: 10.1%- 12.4%) at one year, 16.3% (95% CI: 15.1%-17.6%) at three years, 19.8% (95% CI: 18.5%-21.2%) at five years and 23.3% (95% CI: 21.6-25.1) at ten years. Male sex and low baseline body mass index (BMI) were associated with increased attrition. Factors independently associated with mortality included a low baseline CD4 count, older age, male sex, low baseline BMI and hepatitis B co-infection. Individuals aged above 40 years old had an increased risk of mortality but were less likely to LTFU. There were a total of 137 individuals with first line ART failure starting second line treatment. The probability of first line failure was estimated at 2.8% (95% CI: 2.3%-3.4%) at 3 years, 4.6% (95% CI: 3.9%-5.5%) at 5 years and 7.8% (95% CI 4.8%-12.5%) at ten years of ART. The probability was particularly high in the first few program years. A lower risk was observed among individuals starting ART during the 2006-2008 period. Factors independently associated with an increased risk of treatment failure included ART-experience, NVP-based ART and a baseline CD4 count below 200 cells/μL.

CONCLUSIONS

Overall program outcomes were fair, and generally compare well to other reports from the region. Despite gradually earlier initiation of ART over the ten year period, ART is still initiated at too low CD4 count levels, warranting increased efforts for early HIV diagnosis and enrolment/retention into HIV care. Tailored strategies for poor prognostic groups (older age, male, low BMI) should be designed and evaluated.

摘要

背景

尽管开始抗逆转录病毒治疗(ART)时的HIV疾病阶段是决定ART治疗效果的关键因素,但在亚洲,很少有报告对这一情况进行纵向监测。利用柬埔寨金边市西哈努克医院中心希望项目前瞻性收集的大型ART项目数据,我们报告了十年间患者特征和治疗效果的变化情况。

方法

我们进行了一项回顾性分析,纳入了2003年3月至2013年3月在柬埔寨金边市一家非政府医院开始接受ART治疗的所有成年人(≥18岁)。采用Kaplan-Meier方法计算死亡、失访(LTFU)、减员(死亡或LTFU)和一线治疗失败的累积发生率。使用Cox回归模型确定这些治疗效果的独立危险因素。

结果

在这十年间,3581名患者开始接受ART治疗,中位随访时间为4.8年(四分位间距2.8 - 7.2年)。中位年龄为35岁(四分位间距30 - 41岁),54%为女性。开始ART治疗时的中位CD4细胞计数从2003年的22个/μL(四分位间距4 - 129个/μL)增加到2013年的218个/μL(四分位间距57 - 302个/μL)。在这10年期间,共有282人(7.9%)死亡,433人(12.1%)被定义为失访。项目减员(死亡或失访)在1年时为11.1%(95%置信区间:10.1% - 12.4%),3年时为16.3%(95%置信区间:15.1% - 17.6%),5年时为19.8%(95%置信区间:18.5% - 21.2%),10年时为23.3%(95%置信区间:21.6% - 25.1%)。男性和低基线体重指数(BMI)与减员增加相关。与死亡率独立相关的因素包括低基线CD4细胞计数、年龄较大、男性、低基线BMI和乙肝合并感染。40岁以上的个体死亡风险增加,但失访可能性较小。共有137人一线ART治疗失败并开始二线治疗。一线治疗失败的概率在ART治疗3年时估计为2.8%(95%置信区间:2.3% - 3.4%),5年时为4.6%(95%置信区间:3.9% - 5.5%),10年时为7.8%(95%置信区间4.8% - 12.5%)。在项目开展的最初几年概率尤其高。在2006 - 2008年期间开始接受ART治疗的个体中观察到较低的风险。与治疗失败风险增加独立相关的因素包括ART治疗经验、基于奈韦拉平的ART方案以及基线CD4细胞计数低于200个/μL。

结论

总体项目治疗效果尚可,总体上与该地区的其他报告相比情况较好。尽管在这十年间ART治疗开始时间逐渐提前,但仍在CD4细胞计数过低时开始治疗,有必要加大力度进行早期HIV诊断以及让患者加入/留在HIV治疗体系中。应为预后较差的群体(年龄较大、男性、低BMI)设计并评估针对性策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc5a/5685593/54f3e29ed2da/pone.0185348.g001.jpg

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