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马拉维利隆圭中断抗逆转录病毒治疗后患者的病毒学失败和耐药性。

Virological failure and drug resistance in patients on antiretroviral therapy after treatment interruption in Lilongwe, Malawi.

机构信息

Institute of Public Health, University of Heidelberg, Germany.

出版信息

Clin Infect Dis. 2012 Aug;55(3):441-8. doi: 10.1093/cid/cis438. Epub 2012 May 9.

Abstract

BACKGROUND

Since 2004, Malawi has rapidly scaled up access to antiretroviral therapy (ART) in the national program following a public health approach with limited laboratory monitoring. We examined virological outcomes in patients with treatment interruption at 2 clinics of the Lighthouse Trust, Lilongwe, Malawi.

METHODS

We evaluated patients who resumed first-line ART after having at least 1 treatment interruption documented in the electronic data system in 2008-2009. Viral load (VL) was analyzed at least 2 months after resumption of ART. For VL ≥1000 copies/mL, drug-resistance genotype was characterized using the Stanford database.

RESULTS

Between June and November 2009, we enrolled 133 patients (58.7% female) with a mean age of 38.4 years. Mean duration of ART prior to treatment interruption was 14.3 months. After a minimum of 2 months following ART resumption, VL was undetectable in 81 (60.9%) patients, was 400-1000 copies/mL in 12 (9.0%) patients, and was ≥1000 copies/mL in 40 (30.1%) patients. Genotyping and drug-resistance testing were successfully performed for 36 of 40 patients, all carrying human immunodeficiency virus type 1 subtype C. Relevant mutations affecting nonnucleoside reverse transcriptase inhibitors were found in 32 of 133 (24.1%) patients and combined with relevant nucleoside reverse transcriptase mutations in 27 of 133 (20.3%) patients.

CONCLUSIONS

Virological failure combined with drug resistance after resumption of first-line ART occurred in 24.1% of the patients with treatment interruption, requiring a switch to protease inhibitor-based second-line therapy. Patients with treatment interruption should receive VL assessment after resumption of ART to detect treatment failure and to reduce development and spread of drug resistance.

摘要

背景

自 2004 年以来,马拉维在国家规划中采用公共卫生方法,以有限的实验室监测为手段,迅速扩大了抗逆转录病毒疗法(ART)的可及性。我们在马拉维利隆圭的灯塔信托(Lighthouse Trust)的 2 个诊所,对治疗中断的患者进行了病毒学结局检测。

方法

我们评估了 2008-2009 年电子数据系统中至少记录了 1 次治疗中断的患者,这些患者在恢复一线 ART 后至少 2 个月时进行了病毒载量(VL)检测。对于 VL≥1000 拷贝/ml 的患者,使用斯坦福数据库对耐药基因型进行了特征分析。

结果

2009 年 6 月至 11 月,我们共纳入了 133 名(58.7%为女性)患者,平均年龄为 38.4 岁。治疗中断前接受 ART 的平均时间为 14.3 个月。在恢复 ART 后至少 2 个月时,81 名(60.9%)患者的 VL 不可检测,12 名(9.0%)患者的 VL 为 400-1000 拷贝/ml,40 名(30.1%)患者的 VL≥1000 拷贝/ml。对 40 名患者中的 36 名成功进行了基因分型和耐药性检测,所有患者均携带人类免疫缺陷病毒 1 型亚型 C。在 133 名患者中,有 32 名(24.1%)患者发现了影响非核苷类逆转录酶抑制剂的相关突变,有 27 名(20.3%)患者发现了与核苷类逆转录酶突变相结合的相关突变。

结论

中断一线 ART 后恢复治疗时出现病毒学失败和耐药的患者占 24.1%,需要转为基于蛋白酶抑制剂的二线治疗。中断治疗的患者在恢复 ART 后应进行 VL 评估,以检测治疗失败,并减少耐药性的发展和传播。

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