Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich, Munich, Germany.
German Center for Infection Research, Partner site Munich, Munich, Germany.
Trop Med Int Health. 2020 May;25(5):579-589. doi: 10.1111/tmi.13373. Epub 2020 Feb 6.
Early identification of confirmed virological failure is paramount to avoid accumulation of drug resistance in patients on antiretroviral therapy (ART). Scale-up of HIV-RNA monitoring in Africa and timely switch to second-line regimens are challenged.
A WHO adapted confirmed virological treatment screening algorithm (HIV-RNA screening, enhanced adherence counselling, confirmatory HIV-RNA testing) was evaluated in HIV-infected patients on first-line ART from Tanzania. The main endpoints included viral resuppression and virological failure rates, retention and turnaround time of the screening algorithm until second-line ART initiation. Secondary endpoints included risk factors for virological treatment failure and patterns of genotypic drug resistance.
HIV-RNA >1000 copies/ml at first screening was detected in 58/356 (16.3%) patients (median time-on-treatment 6.3 years, 25% immunological treatment failure). Adjusted risk factors for virological failure were age <30 years (RR 5.2 [95% CI: 2.5-10.8]), years on ART ≥3 years (RR 3.0 [1.0-8.9]), CD4-counts <200 cells/µl (RR 9.3 [4.0-21.8]) and poor self-reported treatment adherence (RR 2.0 [1.2-3.4]). Resuppression of HIV-RNA <1000 copies/ml was observed in 5/50 (10%) cases after enhanced adherence counselling. Confirmatory testing within 3 months was performed in only 46.6% and switch to second-line ART within 6 months in 60.4% of patients. Major NNRTI-mutation were detected in all of 30 patients, NRTI mutations in 96.7% and ≥3 thymidine-analogue mutations in 40%. No remaining NRTI options were predicted in 57% and limited susceptibility in 23% of patients.
We observed low levels of viral resuppression following adherence counselling, associated with high levels of accumulated drug resistance. High visit burden and turnaround times for confirmed virological failure diagnosis further delayed switching to second-line treatment which could be improved using novel point-of-care viral load monitoring systems.
早期发现确证的病毒学失败对于避免接受抗逆转录病毒治疗(ART)的患者产生耐药至关重要。在非洲扩大 HIV-RNA 监测并及时转为二线治疗方案面临挑战。
我们评估了在坦桑尼亚接受一线 ART 的 HIV 感染者中使用世界卫生组织(WHO)改编的确证性病毒学治疗筛查算法(HIV-RNA 筛查、增强型依从性咨询、确证性 HIV-RNA 检测)。主要终点包括病毒学抑制的恢复和病毒学失败率、筛查算法直至二线治疗开始的保留率和周转时间。次要终点包括病毒学治疗失败的危险因素和基因型耐药模式。
首次筛查时发现 58/356(16.3%)名患者的 HIV-RNA>1000 拷贝/ml(中位治疗时间 6.3 年,25%免疫治疗失败)。病毒学失败的调整后危险因素包括年龄<30 岁(RR 5.2 [95%CI:2.5-10.8])、ART 治疗时间≥3 年(RR 3.0 [1.0-8.9])、CD4 计数<200 个/µl(RR 9.3 [4.0-21.8])和自我报告的治疗依从性差(RR 2.0 [1.2-3.4])。增强依从性咨询后,5/50(10%)例患者的 HIV-RNA 恢复到<1000 拷贝/ml。仅 46.6%的患者在 3 个月内进行了确认性检测,60.4%的患者在 6 个月内转为二线治疗。30 名患者均检测到主要 NNRTI 突变,96.7%的患者检测到 NRTI 突变,40%的患者检测到≥3 种胸苷类似物突变。57%的患者预测无剩余 NRTI 选择,23%的患者预测耐药性有限。
我们观察到增强依从性咨询后病毒学抑制水平较低,与耐药性的积累水平较高有关。确认性病毒学失败诊断的高就诊负担和周转时间进一步延迟了二线治疗的转换,使用新型即时病毒载量监测系统可改善这一情况。