The combined effect of modern highly active antiretroviral therapy regimens and adherence on mortality over time.
The combined effect of modern highly active antiretroviral therapy regimens and adherence on mortality over time.
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DOI：
10.1097/qai.0b013e31819675e9
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发表时间：
2009-04-15
期刊：
影响因子：
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通讯作者：
Montaner JS
中科院分区：
文献类型：
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作者：
Lima VD;Harrigan R;Bangsberg DR;Hogg RS;Gross R;Yip B;Montaner JS
描述纵向依从性对开始目前推荐的高效抗逆转录病毒治疗（HAART）方案的初用药个体生存的影响。符合条件的研究参与者在2000年1月至2004年11月期间开始HAART治疗，随访至2005年11月（N = 903）。HAART方案包含依非韦伦、奈韦拉平或利托那韦增强的阿扎那韦或洛匹那韦。边际结构建模用于解决我们的目标。全因死亡率为11%。随着时间的推移，个体依从性显著下降，平均依从性从开始HAART治疗的前6个月内的79%下降到24至30个月内的72% （P值< 0.01）。随着时间的推移，不依从性（<95%）与较高的死亡率密切相关（风险比：3.13；95%可信区间（CI）： 1.95至5.05）。非核苷逆转录酶抑制剂（NNRTI）和增强蛋白酶抑制剂方案的非粘附（<95%）患者的死亡率分别是粘附患者的3.61倍（95% CI: 2.15至6.06）和3.25倍（95% CI: 1.63至6.49）。在以nnrti为基础的治疗方案中，未坚持服用依非韦伦的患者死亡率更高。随着时间的推移，不完全坚持现代HAART治疗与死亡率增加密切相关，而接受以依非韦伦为基础的NNRTI治疗的患者如果不坚持治疗，风险尤其更高。这些结果强调需要制定进一步的战略，以帮助长期维持高水平的依从性。
To characterize the impact of longitudinal adherence on survival in drug-naive individuals starting currently recommended highly active antiretroviral therapy (HAART) regimens. Eligible study participants initiated HAART between January 2000 and November 2004 and were followed until November 2005 (N = 903). HAART regimens contained efavirenz, nevirapine, or ritonavir-boosted atazanavir or lopinavir. Marginal structural modeling was used to address our objective. The all-cause mortality was 11%. Individual adherence decreased significantly over time, with the mean adherence shifting from 79% within the first 6 months of starting HAART to 72% within the 24- to 30-month period (P value < 0.01). Nonadherence over time (<95%) was strongly associated with higher risk of mortality (hazard ratio: 3.13; 95% confidence interval (CI): 1.95 to 5.05). Nonadherent (<95%) patients on nonnucleoside reverse transcriptase inhibitor (NNRTI)–based and boosted protease inhibitor–based regimens were, respectively, 3.61 times (95% CI: 2.15 to 6.06) and 3.25 times (95% CI: 1.63 to 6.49) more likely to die than adherent patients. Within the NNRTI-based regimens, nonadherent individuals on efavirenz were at a higher risk of mortality. Incomplete adherence to modern HAART over time was strongly associated with increased mortality, and patients on efavirenz-based NNRTI therapies were particularly at a higher risk if nonadherent. These results highlight the need to develop further strategies to help sustain high levels of adherence on a long-term basis.