Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
J Int AIDS Soc. 2018 Jan;21(1). doi: 10.1002/jia2.25031.
HIV-1 infection leads to chronic inflammation and to an increased risk of non-AIDS mortality. Our objective was to determine whether AIDS-defining events (ADEs) were associated with increased overall and cause-specific non-AIDS related mortality after antiretroviral therapy (ART) initiation.
We included HIV treatment-naïve adults from the Antiretroviral Therapy Cohort Collaboration (ART-CC) who initiated ART from 1996 to 2014. Causes of death were assigned using the Coding Causes of Death in HIV (CoDe) protocol. The adjusted hazard ratio (aHR) for overall and cause-specific non-AIDS mortality among those with an ADE (all ADEs, tuberculosis (TB), Pneumocystis jiroveci pneumonia (PJP), and non-Hodgkin's lymphoma (NHL)) compared to those without an ADE was estimated using a marginal structural model.
The adjusted hazard of overall non-AIDS mortality was higher among those with any ADE compared to those without any ADE (aHR 2.21, 95% confidence interval (CI) 2.00 to 2.43). The adjusted hazard of each of the cause-specific non-AIDS related deaths were higher among those with any ADE compared to those without, except metabolic deaths (malignancy aHR 2.59 (95% CI 2.13 to 3.14), accident/suicide/overdose aHR 1.37 (95% CI 1.05 to 1.79), cardiovascular aHR 1.95 (95% CI 1.54 to 2.48), infection aHR (95% CI 1.68 to 2.81), hepatic aHR 2.09 (95% CI 1.61 to 2.72), respiratory aHR 4.28 (95% CI 2.67 to 6.88), renal aHR 5.81 (95% CI 2.69 to 12.56) and central nervous aHR 1.53 (95% CI 1.18 to 5.44)). The risk of overall and cause-specific non-AIDS mortality differed depending on the specific ADE of interest (TB, PJP, NHL).
In this large multi-centre cohort collaboration with standardized assignment of causes of death, non-AIDS mortality was twice as high among patients with an ADE compared to without an ADE. However, non-AIDS related mortality after an ADE depended on the ADE of interest. Although there may be unmeasured confounders, these findings suggest that a common pathway may be independently driving both ADEs and NADE mortality. While prevention of ADEs may reduce subsequent death due to NADEs following ART initiation, modification of risk factors for NADE mortality remains important after ADE survival.
HIV-1 感染会导致慢性炎症，并增加非艾滋病相关死亡率的风险。我们的目的是确定艾滋病定义事件（ADE）是否与抗逆转录病毒治疗（ART）后整体和特定原因的非艾滋病相关死亡率增加有关。
我们纳入了来自抗逆转录病毒治疗队列合作（ART-CC）的 HIV 治疗初治成年人，他们于 1996 年至 2014 年开始接受 ART。使用 HIV 死因编码（CoDe）方案对死因进行分类。使用边缘结构模型估计有 ADE（所有 ADE、结核病（TB）、卡氏肺孢子虫肺炎（PJP）和非霍奇金淋巴瘤（NHL））与无 ADE 的患者相比，整体和特定原因非艾滋病死亡率的调整后的风险比（aHR）。
与无任何 ADE 的患者相比，任何 ADE 的患者整体非艾滋病死亡率的调整风险更高（aHR 2.21，95%置信区间（CI）2.00 至 2.43）。与无任何 ADE 的患者相比，每种特定原因的非艾滋病相关死亡的调整风险均较高，除代谢死亡（恶性肿瘤 aHR 2.59（95%CI 2.13 至 3.14），意外/自杀/过量 aHR 1.37（95%CI 1.05 至 1.79），心血管 aHR 1.95（95%CI 1.54 至 2.48），感染 aHR（95%CI 1.68 至 2.81），肝 aHR 2.09（95%CI 1.61 至 2.72），呼吸 aHR 4.28（95%CI 2.67 至 6.88），肾 aHR 5.81（95%CI 2.69 至 12.56）和中枢神经系统 aHR 1.53（95%CI 1.18 至 5.44））。整体和特定原因非艾滋病死亡率的风险取决于特定的 ADE（TB、PJP、NHL）。
在这项涉及大量多中心队列的合作研究中，使用标准化的死因分配方法，与无 ADE 的患者相比，有 ADE 的患者的非艾滋病死亡率高两倍。然而，ADE 后的非艾滋病相关死亡率取决于所关注的 ADE。尽管可能存在未测量的混杂因素，但这些发现表明，共同途径可能独立地驱动 ADE 和非 ADE 死亡率。虽然预防 ADE 可能会降低 ART 后因非 ADE 而导致的后续死亡，但在 ADE 存活后，仍然需要改变非 ADE 死亡率的危险因素。
