Achhra A C, Phillips A, Emery S, MacArthur R D, Furrer H, De Wit S, Losso M, Law M G
Kirby Institute, UNSW Australia, Sydney, NSW, Australia.
Research Department of Infection & Population Health, University College London, London, UK.
HIV Med. 2015 Aug;16(7):449-54. doi: 10.1111/hiv.12258. Epub 2015 May 11.
Pre-antiretroviral therapy (ART) inflammation and coagulation activation predict clinical outcomes in HIV-positive individuals. We assessed whether pre-ART inflammatory marker levels predicted the CD4 count response to ART.
Analyses were based on data from the Strategic Management of Antiretroviral Therapy (SMART) trial, an international trial evaluating continuous vs. interrupted ART, and the Flexible Initial Retrovirus Suppressive Therapies (FIRST) trial, evaluating three first-line ART regimens with at least two drug classes. For this analysis, participants had to be ART-naïve or off ART at randomization and (re)starting ART and have C-reactive protein (CRP), interleukin-6 (IL-6) and D-dimer measured pre-ART. Using random effects linear models, we assessed the association between each of the biomarker levels, categorized as quartiles, and change in CD4 count from ART initiation to 24 months post-ART. Analyses adjusted for CD4 count at ART initiation (baseline), study arm, follow-up time and other known confounders.
Overall, 1084 individuals [659 from SMART (26% ART naïve) and 425 from FIRST] met the eligibility criteria, providing 8264 CD4 count measurements. Seventy-five per cent of individuals were male with the mean age of 42 years. The median (interquartile range) baseline CD4 counts were 416 (350-530) and 100 (22-300) cells/μL in SMART and FIRST, respectively. All of the biomarkers were inversely associated with baseline CD4 count in FIRST but not in SMART. In adjusted models, there was no clear relationship between changing biomarker levels and mean change in CD4 count post-ART (P for trend: CRP, P = 0.97; IL-6, P = 0.25; and D-dimer, P = 0.29).
Pre-ART inflammation and coagulation activation do not predict CD4 count response to ART and appear to influence the risk of clinical outcomes through other mechanisms than blunting long-term CD4 count gain.
抗逆转录病毒治疗（ART）前的炎症和凝血激活可预测HIV阳性个体的临床结局。我们评估了ART前炎症标志物水平是否能预测ART治疗后的CD4细胞计数反应。
分析基于抗逆转录病毒治疗战略管理（SMART）试验和灵活初始逆转录病毒抑制疗法（FIRST）试验的数据。SMART试验是一项评估持续与间断ART的国际试验，FIRST试验评估了三种至少包含两类药物的一线ART方案。在本次分析中，参与者在随机分组时必须未接受过ART或已停用ART且正在（重新）开始ART治疗，并在ART前检测了C反应蛋白（CRP）、白细胞介素-6（IL-6）和D-二聚体。使用随机效应线性模型，我们评估了按四分位数分类的每种生物标志物水平与ART开始至ART后24个月CD4细胞计数变化之间的关联。分析对ART开始时（基线）的CD4细胞计数、研究组、随访时间和其他已知混杂因素进行了校正。
总体而言，1084名个体[659名来自SMART试验（26%未接受过ART）和425名来自FIRST试验]符合纳入标准，并提供了8264次CD4细胞计数测量数据。75%的个体为男性，平均年龄42岁。SMART试验和FIRST试验中基线CD4细胞计数的中位数（四分位间距）分别为416（350 - 530）和100（22 - 300）个/μL。在FIRST试验中，所有生物标志物均与基线CD4细胞计数呈负相关，但在SMART试验中并非如此。在校正模型中，生物标志物水平变化与ART后CD4细胞计数的平均变化之间没有明确关系（趋势P值：CRP，P = 0.97；IL-6，P = 0.25；D-二聚体，P = 0.29）。
ART前的炎症和凝血激活不能预测ART治疗后的CD4细胞计数反应，且似乎通过除减弱长期CD4细胞计数增加之外的其他机制影响临床结局风险。
