Hospital La Paz Institute for Health Research, Madrid, Spain.
Institute of Health Carlos III, Madrid, Spain.
J Infect Dis. 2018 Oct 5;218(10):1523-1530. doi: 10.1093/infdis/jiy399.
Tenofovir is a potent inhibitor of human telomerase. The clinical relevance of this inhibition is unknown.
NEAT001/ANRS143 is a randomized trial that showed noninferiority over 96 weeks of ritonavir-boosted darunavir plus raltegravir versus tenofovir disoproxil fumarate/emtricitabine in 805 antiretroviral antiretrovrial-naive HIV-infected adults. We compared changes in whole-blood telomere length measured with quantitative polymerase chain reaction in 201 randomly selected participants (104 raltegravir and 97 tenofovir disoproxil fumarate/emtricitabine). We performed multivariable estimative and predictive linear regression.
At week 96, participants receiving tenofovir disoproxil fumarate/emtricitabine had a statistically significant higher gain in telomere length than participants receiving raltegravir. Difference in mean telomere length change between groups (tenofovir disoproxil fumarate/emtricitabine minus raltegravir) from baseline to week 96 adjusted by baseline telomere length was 0.031 (P = .009). This difference was not significantly confounded by age, gender, known duration of HIV infection, CD4 (baseline/nadir), CD8 cells, CD4/CD8 ratio, HIV viral load (baseline/week 96), tobacco and alcohol consumption, statins, or hepatitis C.
Antiretroviral-naive HIV-infected adults receiving ritonavir-boosted darunavir and tenofovir disoproxil fumarate/emtricitabine had a significant higher gain in blood telomere length than those receiving ritonavir-boosted darunavir and raltegravir, suggesting a better initial recovery from HIV-associated immunosenescence.
替诺福韦是一种有效的人类端粒酶抑制剂。这种抑制的临床相关性尚不清楚。
NEAT001/ANRS143 是一项随机试验,该试验显示在 96 周的时间里,利托那韦增强的达芦那韦加雷特曲韦与富马酸替诺福韦二吡呋酯/恩曲他滨相比,在 805 名未经抗逆转录病毒治疗的 HIV 感染的成年患者中具有非劣效性。我们比较了在 201 名随机选择的参与者(104 名雷特格韦和 97 名富马酸替诺福韦二吡呋酯/恩曲他滨)的全血端粒长度用定量聚合酶链反应测量的变化。我们进行了多变量估计和预测线性回归。
在第 96 周时,接受富马酸替诺福韦二吡呋酯/恩曲他滨治疗的参与者的端粒长度增长明显高于接受雷特格韦治疗的参与者。从基线到第 96 周,两组间端粒长度变化的平均差异(富马酸替诺福韦二吡呋酯/恩曲他滨减去雷特格韦),通过基线端粒长度调整,为 0.031(P =.009)。这种差异不受年龄、性别、已知的 HIV 感染时间、CD4(基线/最低点)、CD8 细胞、CD4/CD8 比值、HIV 病毒载量(基线/第 96 周)、烟草和酒精消耗、他汀类药物或丙型肝炎的显著混杂。
接受利托那韦增强的达芦那韦和富马酸替诺福韦二吡呋酯/恩曲他滨治疗的未经抗逆转录病毒治疗的 HIV 感染的成年患者的血液端粒长度增长明显高于接受利托那韦增强的达芦那韦和雷特格韦治疗的患者,这表明从 HIV 相关免疫衰老中恢复的初始情况更好。