PDF(Pubmed)
Abstract：
UNASSIGNED: Understanding and identifying the immunological markers and clinical information linked with HIV acquisition is crucial for effectively implementing Pre-Exposure Prophylaxis (PrEP) to prevent HIV acquisition. Prior analysis on HIV incidence outcomes have predominantly employed proportional hazards (PH) models, adjusting solely for baseline covariates. Therefore, models that integrate cytokine biomarkers, particularly as time-varying covariates, are sorely needed.
UNASSIGNED: We built a simple model using the Cox PH to investigate the impact of specific cytokine profiles in predicting the overall HIV incidence. Further, Kaplan-Meier curves were used to compare HIV incidence rates between the treatment and placebo groups while assessing the overall treatment effectiveness. Utilizing stepwise regression, we developed a series of Cox PH models to analyze 48 longitudinally measured cytokine profiles. We considered three kinds of effects in the cytokine profile measurements: average, difference, and time-dependent covariate. These effects were combined with baseline covariates to explore their influence on predictors of HIV incidence.
UNASSIGNED: Comparing the predictive performance of the Cox PH models developed using the AIC metric, model 4 (Cox PH model with time-dependent cytokine) outperformed the others. The results indicated that the cytokines, interleukin (IL-2, IL-3, IL-5, IL-10, IL-16, IL-12P70, and IL-17 alpha), stem cell factor (SCF), beta nerve growth factor (B-NGF), tumor necrosis factor alpha (TNF-A), interferon (IFN) alpha-2, serum stem cell growth factor (SCG)-beta, platelet-derived growth factor (PDGF)-BB, granulocyte macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and cutaneous T-cell-attracting chemokine (CTACK) were significantly associated with HIV incidence. Baseline predictors significantly associated with HIV incidence when considering cytokine effects included: age of oldest sex partner, age at enrollment, salary, years with a stable partner, sex partner having any other sex partner, husband\'s income, other income source, age at debut, years lived in Durban, and sex in the last 30 days.
UNASSIGNED: Overall, the inclusion of cytokine effects enhanced the predictive performance of the models, and the PrEP group exhibited reduced HIV incidences compared to the placebo group.
UNASSIGNED: We built a simple model using the Cox PH to investigate the impact of specific cytokine profiles in predicting the overall HIV incidence. Further, Kaplan-Meier curves were used to compare HIV incidence rates between the treatment and placebo groups while assessing the overall treatment effectiveness. Utilizing stepwise regression, we developed a series of Cox PH models to analyze 48 longitudinally measured cytokine profiles. We considered three kinds of effects in the cytokine profile measurements: average, difference, and time-dependent covariate. These effects were combined with baseline covariates to explore their influence on predictors of HIV incidence.
UNASSIGNED: Comparing the predictive performance of the Cox PH models developed using the AIC metric, model 4 (Cox PH model with time-dependent cytokine) outperformed the others. The results indicated that the cytokines, interleukin (IL-2, IL-3, IL-5, IL-10, IL-16, IL-12P70, and IL-17 alpha), stem cell factor (SCF), beta nerve growth factor (B-NGF), tumor necrosis factor alpha (TNF-A), interferon (IFN) alpha-2, serum stem cell growth factor (SCG)-beta, platelet-derived growth factor (PDGF)-BB, granulocyte macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and cutaneous T-cell-attracting chemokine (CTACK) were significantly associated with HIV incidence. Baseline predictors significantly associated with HIV incidence when considering cytokine effects included: age of oldest sex partner, age at enrollment, salary, years with a stable partner, sex partner having any other sex partner, husband\'s income, other income source, age at debut, years lived in Durban, and sex in the last 30 days.
UNASSIGNED: Overall, the inclusion of cytokine effects enhanced the predictive performance of the models, and the PrEP group exhibited reduced HIV incidences compared to the placebo group.
摘要：
■了解和确定与HIV感染相关的免疫学标记和临床信息对于有效实施暴露前预防（PrEP）以防止HIV感染至关重要。先前对艾滋病毒发病率结果的分析主要采用比例风险(PH)模型，仅对基线协变量进行调整。因此,整合细胞因子生物标志物的模型，特别是作为时变协变量，非常需要。
■我们使用CoxPH建立了一个简单的模型，以研究特定细胞因子谱在预测总体HIV发病率中的影响。Further,使用Kaplan-Meier曲线比较治疗组和安慰剂组之间的HIV发病率,同时评估总体治疗效果。利用逐步回归，我们开发了一系列CoxPH模型来分析48个纵向测量的细胞因子谱.我们在细胞因子谱测量中考虑了三种效应：平均，差异,和时间依赖的协变量。将这些效应与基线协变量相结合，以探索它们对HIV发病率预测因子的影响。
■比较使用AIC度量开发的CoxPH模型的预测性能，模型4(具有时间依赖性细胞因子的CoxPH模型)优于其他模型。结果表明，细胞因子，白细胞介素（IL-2，IL-3，IL-5，IL-10，IL-16，IL-12P70和IL-17α），干细胞因子（SCF），β神经生长因子(B-NGF),肿瘤坏死因子α（TNF-A），干扰素（IFN）α-2，血清干细胞生长因子（SCG）-β，血小板衍生生长因子（PDGF）-BB，粒细胞巨噬细胞集落刺激因子（GM-CSF），肿瘤坏死因子相关凋亡诱导配体(TRAIL),皮肤T细胞吸引趋化因子(CTACK)与HIV发病率显著相关.考虑细胞因子效应时，基线预测因子与HIV发病率显着相关，包括：年龄最大的性伴侣的年龄，入学年龄，薪水,多年来有一个稳定的合作伙伴，有其他性伴侣的性伴侣,丈夫的收入，其他收入来源，首次亮相的年龄，在德班生活了几年，在过去的30天里做爱.
■总的来说，纳入细胞因子效应增强了模型的预测性能，与安慰剂组相比，PrEP组的HIV发病率降低。
■我们使用CoxPH建立了一个简单的模型，以研究特定细胞因子谱在预测总体HIV发病率中的影响。Further,使用Kaplan-Meier曲线比较治疗组和安慰剂组之间的HIV发病率,同时评估总体治疗效果。利用逐步回归，我们开发了一系列CoxPH模型来分析48个纵向测量的细胞因子谱.我们在细胞因子谱测量中考虑了三种效应：平均，差异,和时间依赖的协变量。将这些效应与基线协变量相结合，以探索它们对HIV发病率预测因子的影响。
■比较使用AIC度量开发的CoxPH模型的预测性能，模型4(具有时间依赖性细胞因子的CoxPH模型)优于其他模型。结果表明，细胞因子，白细胞介素（IL-2，IL-3，IL-5，IL-10，IL-16，IL-12P70和IL-17α），干细胞因子（SCF），β神经生长因子(B-NGF),肿瘤坏死因子α（TNF-A），干扰素（IFN）α-2，血清干细胞生长因子（SCG）-β，血小板衍生生长因子（PDGF）-BB，粒细胞巨噬细胞集落刺激因子（GM-CSF），肿瘤坏死因子相关凋亡诱导配体(TRAIL),皮肤T细胞吸引趋化因子(CTACK)与HIV发病率显著相关.考虑细胞因子效应时，基线预测因子与HIV发病率显着相关，包括：年龄最大的性伴侣的年龄，入学年龄，薪水,多年来有一个稳定的合作伙伴，有其他性伴侣的性伴侣,丈夫的收入，其他收入来源，首次亮相的年龄，在德班生活了几年，在过去的30天里做爱.
■总的来说，纳入细胞因子效应增强了模型的预测性能，与安慰剂组相比，PrEP组的HIV发病率降低。
