Petersen Maya L, Tran Linh, Geng Elvin H, Reynolds Steven J, Kambugu Andrew, Wood Robin, Bangsberg David R, Yiannoutsos Constantin T, Deeks Steven G, Martin Jeffrey N
AIDS. 2014 Sep 10;28(14):2097-107. doi: 10.1097/QAD.0000000000000349.
Routine monitoring of plasma HIV RNA among HIV-infected patients on antiretroviral therapy (ART) is unavailable in many resource-limited settings. Alternative monitoring approaches correlate poorly with virologic failure and can substantially delay switch to second-line therapy. We evaluated the impact of delayed switch on mortality among patients with virologic failure in Africa.
A cohort.
We examined patients with confirmed virologic failure on first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens from four cohorts with serial HIV RNA monitoring in Uganda and South Africa. Marginal structural models aimed to estimate the effect of delayed switch on mortality in a hypothetical trial in which switch time was randomly assigned. Inverse probability weights adjusted for measured confounders including time-updated CD4+ T-cell count and HIV RNA. Results: Among 823 patients with confirmed virologic failure, the cumulative incidence of switch 180 days after failure was 30% [95% confidence interval (CI) 27-33]. The majority of patients (74%) had not failed immunologically as defined by WHO criteria by the time of virologic failure. Adjusted mortality was higher for individuals who remained on first-line therapy than for those who had switched [odds ratio (OR) 2.1, 95% CI 1.1-4.2]. Among those without immunologic failure, the relative harm of failure to switch was similar (OR 2.4; 95% CI 0.99-5.8) to that of the entire cohort, although of borderline statistical significance.
Among HIV-infected patients with confirmed virologic failure on first-line ART, remaining on first-line therapy led to an increase in mortality relative to switching. Our results suggest that detection and response to confirmed virologic failure could decrease mortality.
在许多资源有限的环境中，无法对接受抗逆转录病毒治疗（ART）的HIV感染患者进行血浆HIV RNA的常规监测。替代监测方法与病毒学失败的相关性较差，并且可能会大幅延迟二线治疗的转换。我们评估了非洲病毒学失败患者延迟转换治疗对死亡率的影响。
队列研究。
我们检查了来自乌干达和南非的四个队列中接受基于一线非核苷类逆转录酶抑制剂（NNRTI）方案治疗且病毒学失败得到确认的患者，这些队列进行了连续的HIV RNA监测。边际结构模型旨在估计在假设的随机分配转换时间的试验中延迟转换治疗对死亡率的影响。逆概率权重针对包括时间更新的CD4 + T细胞计数和HIV RNA在内的测量混杂因素进行了调整。结果：在823例病毒学失败得到确认的患者中，失败后180天转换治疗的累积发生率为30%[95%置信区间（CI）27 - 33]。大多数患者（74%）在病毒学失败时未达到世界卫生组织标准定义的免疫失败。一线治疗组患者的校正死亡率高于转换治疗组患者[优势比（OR）2.1，95%CI 1.1 - 4.2]。在没有免疫失败的患者中，未转换治疗的相对危害与整个队列相似（OR 2.4；95%CI 0.99 - 5.8），尽管具有边缘统计学意义。
在接受一线抗逆转录病毒治疗且病毒学失败得到确认的HIV感染患者中，相对于转换治疗，继续接受一线治疗会导致死亡率增加。我们的结果表明，对确认的病毒学失败进行检测和应对可以降低死亡率。
