Comparison of tenofovir, zidovudine, or stavudine as part of first-line antiretroviral therapy in a resource-limited-setting: a cohort study.

Comparison of tenofovir, zidovudine, or stavudine as part of first-line antiretroviral therapy in a resource-limited-setting: a cohort study.
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DOI:
10.1371/journal.pone.0064459
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Hoffmann CJ
Hoffmann CJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Velen K;Lewis JJ;Charalambous S;Grant AD;Churchyard GJ;Hoffmann CJ

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替诺福韦(TDF)是世界卫生组织推荐的一线抗逆转录病毒治疗(ART)的一部分;然而,在资源有限的环境中,将 TDF 与其他核苷逆转录酶抑制剂进行比较的数据有限。我们使用南非的常规工作场所和基于社区的 ART 队列,评估了 TDF、司他夫定 (d4T) 30 mg 剂量和齐多夫定 (AZT) 之间的单一药物替代、HIV RNA 抑制、CD4 计数增加、护理损失和死亡率。在一项前瞻性队列研究中,我们纳入了年龄≥17岁的未接受过ART治疗的患者,他们在2007年至2009年间开始接受含有TDF、d4T或AZT的ART治疗。为了分析单一药物替代,我们使用了竞争风险时间-事件分析;用于护理丧失、混合效应泊松模型;对于 HIV RNA 抑制,竞争风险逻辑回归;对于 CD4 计数斜率,混合效应线性回归;对于死亡率,比例风险模型。在 6,196 名患者中,初始药物为 TDF(665 名(11%))、d4T(4,179 名(68%))和 AZT(1,352 名(22%))。在 ART 的前 6 个月内,与 TDF 相比,d4T 单一药物替代的调整后风险比为 2.3(95% 置信区间 [CI]:0.27, 19),AZT 为 5.2(95% CI:1.1, 23);而 6 个月后,d4T 和 AZT 的该值分别为 10 (95% CI: 5.8, 18) 和 4.4 (95% CI: 2.5, 7.8)。病毒学抑制与药剂相似;然而,AZT 的 CD4 计数上升最低。与 TDF 相比,d4T 的调整后失去护理风险比为 1.5 (95% CI: 1.1, 1.9),AZT 为 1.2 (95% CI: 1.1, 1.4)。与 TDF 相比,d4T 和 AZT 的调整后死亡率风险比分别为 2.7 (95% CI: 2.0, 3.5) 和 1.4 (95% CI: 1.3, 1.5)。在常规护理中,TDF 似乎比 d4T 或 AZT 表现更好,最显着的是,与其他药物相比,药物替代和死亡率更低。
Tenofovir (TDF) is part of the WHO recommended first-line antiretroviral therapy (ART); however, there are limited data comparing TDF to other nucleoside reverse transcriptase inhibitors in resource-limited-settings. Using a routine workplace and community-based ART cohort in South Africa, we assessed single drug substitution, HIV RNA suppression, CD4 count increase, loss-from-care, and mortality between TDF, stavudine (d4T) 30 mg dose, and zidovudine (AZT). In a prospective cohort study we included ART naïve patients aged ≥17 years-old who initiated ART containing TDF, d4T, or AZT between 2007 and 2009. For analysis of single drug substitutions we used a competing-risks time-to-event analysis; for loss-from-care, mixed-effect Poisson modeling; for HIV RNA suppression, competing-risks logistic regression; for CD4 count slope, mixed-effects linear regression; and for mortality, proportional hazards modeling. Of 6,196 patients, the initial drug was TDF for 665 (11%), d4T for 4,179 (68%), and AZT for 1,352 (22%). During the first 6 months of ART, the adjusted hazard ratio for a single drug substitution was 2.3 for d4T (95% confidence interval [CI]: 0.27, 19) and 5.2 for AZT (95% CI: 1.1, 23), compared to TDF; whereas, after 6 months, it was 10 (95% CI: 5.8, 18) and 4.4 (95% CI: 2.5, 7.8) for d4T and AZT, respectively. Virologic suppression was similar by agent; however, CD4 count rise was lowest for AZT. The adjusted hazard ratio for loss-from-care, when compared to TDF, was 1.5 (95% CI: 1.1, 1.9) for d4T and 1.2 (95% CI: 1.1, 1.4) for AZT. The adjusted hazard ratio for mortality, when compared to TDF, was 2.7 (95% CI: 2.0, 3.5) and 1.4 (95% CI: 1.3, 1.5) and for d4T and AZT, respectively. In routine care, TDF appeared to perform better than either d4T or AZT, most notably with less drug substitution and mortality than for either other agent.
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