Institute of Public Health, University of Heidelberg, Germany.
Clin Infect Dis. 2012 Aug;55(3):441-8. doi: 10.1093/cid/cis438. Epub 2012 May 9.
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.
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.
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.
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.
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。
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。
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。
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。