Braun Dominique L, Kouyos Roger, Oberle Corinna, Grube Christina, Joos Beda, Fellay Jacques, McLaren Paul J, Kuster Herbert, Günthard Huldrych F
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne, Switzerland.
PLoS One. 2014 Dec 9;9(12):e114111. doi: 10.1371/journal.pone.0114111. eCollection 2014.
Best long-term practice in primary HIV-1 infection (PHI) remains unknown for the individual. A risk-based scoring system associated with surrogate markers of HIV-1 disease progression could be helpful to stratify patients with PHI at highest risk for HIV-1 disease progression.
We prospectively enrolled 290 individuals with well-documented PHI in the Zurich Primary HIV-1 Infection Study, an open-label, non-randomized, observational, single-center study. Patients could choose to undergo early antiretroviral treatment (eART) and stop it after one year of undetectable viremia, to go on with treatment indefinitely, or to defer treatment. For each patient we calculated an a priori defined "Acute Retroviral Syndrome Severity Score" (ARSSS), consisting of clinical and basic laboratory variables, ranging from zero to ten points. We used linear regression models to assess the association between ARSSS and log baseline viral load (VL), baseline CD4+ cell count, and log viral setpoint (sVL) (i.e. VL measured ≥90 days after infection or treatment interruption).
Mean ARSSS was 2.89. CD4+ cell count at baseline was negatively correlated with ARSSS (p = 0.03, n = 289), whereas HIV-RNA levels at baseline showed a strong positive correlation with ARSSS (p<0.001, n = 290). In the regression models, a 1-point increase in the score corresponded to a 0.10 log increase in baseline VL and a CD4+ cell count decline of 12/µl, respectively. In patients with PHI and not undergoing eART, higher ARSSS were significantly associated with higher sVL (p = 0.029, n = 64). In contrast, in patients undergoing eART with subsequent structured treatment interruption, no correlation was found between sVL and ARSSS (p = 0.28, n = 40).
The ARSSS is a simple clinical score that correlates with the best-validated surrogate markers of HIV-1 disease progression. In regions where ART is not universally available and eART is not standard this score may help identifying patients who will profit the most from early antiretroviral therapy.
对于个体而言,原发性HIV-1感染(PHI)的最佳长期治疗方案仍不明确。一个基于风险且与HIV-1疾病进展替代标志物相关的评分系统,可能有助于对具有最高HIV-1疾病进展风险的PHI患者进行分层。
在苏黎世原发性HIV-1感染研究中,我们前瞻性地招募了290例有充分记录的PHI患者,该研究为开放标签、非随机、观察性单中心研究。患者可选择接受早期抗逆转录病毒治疗(eART),在病毒血症检测不到一年后停药,无限期继续治疗,或推迟治疗。对于每位患者,我们计算了一个预先定义的“急性逆转录病毒综合征严重程度评分”(ARSSS),该评分由临床和基础实验室变量组成,范围从0到10分。我们使用线性回归模型来评估ARSSS与对数基线病毒载量(VL)、基线CD4+细胞计数以及对数病毒设定点(sVL)(即感染或治疗中断后≥90天测得的VL)之间的关联。
ARSSS的平均值为2.89。基线CD4+细胞计数与ARSSS呈负相关(p = 0.03,n = 289),而基线HIV-RNA水平与ARSSS呈强正相关(p<0.001,n = 290)。在回归模型中,评分每增加1分分别对应基线VL对数增加0.10以及CD4+细胞计数下降12/µl。在未接受eART的PHI患者中,较高的ARSSS与较高的sVL显著相关(p = 0.029,n = 64)。相比之下,在接受eART随后进行结构化治疗中断的患者中,未发现sVL与ARSSS之间存在相关性(p = 0.28,n = 40)。
ARSSS是一个简单的临床评分,与HIV-1疾病进展的最佳验证替代标志物相关。在抗逆转录病毒治疗(ART)并非普遍可及且eART并非标准治疗的地区,该评分可能有助于识别那些将从早期抗逆转录病毒治疗中获益最大的患者。