Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich.
AIDS. 2018 Jan 28;32(3):327-335. doi: 10.1097/QAD.0000000000001692.
We estimated and compared the risk of clinically identified acquired drug resistance under immediate initiation [the currently recommended antiretroviral therapy (ART) initiation strategy], initiation with CD4 cell count less than 500 cells/μl and initiation with CD4 cell count less than 350 cells/μl.
Cohort study based on routinely collected data from the HIV-CAUSAL collaboration.
For each individual, baseline was the earliest time when all eligibility criteria (ART-naive, AIDS free, and others) were met after 1999. Acquired drug resistance was defined using the Stanford classification as resistance to any antiretroviral drug that was clinically identified at least 6 months after ART initiation. We used the parametric g-formula to adjust for time-varying (CD4 cell count, HIV RNA, AIDS, ART regimen, and drug resistance testing) and baseline (calendar period, mode of acquisition, sex, age, geographical origin, ethnicity and cohort) characteristics.
In 50 981 eligible individuals, 10% had CD4 cell count more than 500 cells/μl at baseline, and 63% initiated ART during follow-up. Of 2672 tests for acquired drug resistance, 794 found resistance. The estimated 7-year risk (95% confidence interval) of acquired drug resistance was 3.2% (2.8,3.5) for immediate initiation, 3.1% (2.7,3.3) for initiation with CD4 cell count less than 500 cells/μl, and 2.8% (2.5,3.0) for initiation with CD4 cell count less than 350 cells/μl. In analyses restricted to individuals with baseline in 2005-2015, the corresponding estimates were 1.9% (1.8, 2.5), 1.9% (1.7, 2.4), and 1.8% (1.7, 2.2).
Our findings suggest that the risk of acquired drug resistance is very low, especially in recent calendar periods, and that immediate ART initiation only slightly increases the risk. It is unlikely that drug resistance will jeopardize the proven benefits of immediate ART initiation.
我们评估并比较了即刻开始[目前推荐的抗逆转录病毒治疗（ART）启动策略]、CD4 细胞计数<500 个/μl 时开始以及 CD4 细胞计数<350 个/μl 时开始情况下临床发现的获得性耐药的风险。
基于 HIV-CAUSAL 合作收集的常规数据的队列研究。
对于每个个体，基线是在 1999 年后首次满足所有入选标准（ART 初治、无艾滋病且其他标准）的最早时间。获得性耐药定义为在开始 ART 至少 6 个月后临床发现的对任何抗逆转录病毒药物的耐药性，使用斯坦福分类法进行定义。我们使用参数 g 公式来调整时间变化（CD4 细胞计数、HIV RNA、艾滋病、ART 方案和耐药性检测）和基线（日历期、获得途径、性别、年龄、地理来源、种族和队列）特征。
在 50981 名符合条件的个体中，10%的个体基线时 CD4 细胞计数>500 个/μl，63%的个体在随访期间开始接受 ART。在 2672 次获得性耐药检测中，发现了 794 次耐药。即刻开始、CD4 细胞计数<500 个/μl 时开始和 CD4 细胞计数<350 个/μl 时开始的 7 年获得性耐药风险（95%置信区间）估计值分别为 3.2%（2.8，3.5）、3.1%（2.7，3.3）和 2.8%（2.5，3.0）。在仅纳入基线在 2005-2015 年的个体的分析中，相应的估计值分别为 1.9%（1.8，2.5）、1.9%（1.7，2.4）和 1.8%（1.7，2.2）。
我们的研究结果表明，获得性耐药的风险非常低，尤其是在最近的日历时期内，即刻开始 ART 治疗仅略微增加风险。获得性耐药不太可能危及即刻开始 ART 治疗的已证实益处。
