Tinarwo Partson, Zewotir Temesgen, Yende-Zuma Nonhlanhla, Garrett Nigel J, North Delia
School of Mathematics, Statistics and Computer Science, University of KwaZulu-Natal, Durban, South Africa.
Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa.
Infect Dis Ther. 2019 Jun;8(2):269-284. doi: 10.1007/s40121-019-0235-4. Epub 2019 Feb 12.
Past endeavours to deal with the obstacle of expensive Cluster of Difference 4 (CD4) count diagnostics in resource-limited settings have left a long trail of suggested continuous CD4 count clinical covariates that turned out to be a potentially important integral part of the human immunodeficiency virus (HIV) treatment process during disease progression. However, an evaluation to determine the strongest candidates among these CD4 count covariates has not been well documented.
The Centre for the AIDS Programme of Research in South Africa (CAPRISA) initially enrolled HIV-negative (phase 1) patients into different study cohorts. The patients who seroconverted (237) during follow-up care were enrolled again into a post-HIV infection cohort where they were further followed up with weekly to fortnightly visits up to 3 months (phase 2: acute infection), monthly visits from 3-12 months (phase 3: early infection) and quarterly visits thereafter (phase 4: established infection) until antiretroviral therapy (ART) initiation (phase 5). The CD4 count and 46 covariates were repeatedly measured at each phase of the HIV disease progression. A multilevel partial least squares approach was applied as a variable reduction technique to determine the strongest CD4 count covariates.
Only 18 of the 46 investigated clinical attributes were the strongest CD4 count covariates and the top 8 were positively and independently associated with the CD4 count. Besides the confirmatory lymphocytes, these were basophils, albumin, haematocrit, alkaline phosphatase (ALP), mean corpuscular volume (MCV), platelets, potassium and monocytes. Overall, electrolytes, proteins and red blood cells were the dominant categories for the strongest covariates.
Only a few of the many previously suggested continuous CD4 count clinical covariates showed the potential to become an important integral part of the treatment process. Prolonging the pre-treatment period of the HIV disease progression by effectively incorporating and managing the covariates for long-term influence on the CD4 cell response has the potential to delay challenges associated with ART side effects.
过去在资源有限的环境中应对昂贵的差异簇4(CD4)计数诊断障碍的努力,留下了一长串建议的持续CD4计数临床协变量,这些协变量在疾病进展过程中被证明是人类免疫缺陷病毒(HIV)治疗过程中潜在的重要组成部分。然而,尚未有充分记录的评估来确定这些CD4计数协变量中最有力的候选者。
南非艾滋病研究项目中心(CAPRISA)最初将HIV阴性(第1阶段)患者纳入不同的研究队列。在随访期间血清转化的患者(237例)再次被纳入HIV感染后队列,在该队列中,他们每周至每两周进行一次随访,持续3个月(第2阶段:急性感染),3至12个月每月随访一次(第3阶段:早期感染),此后每季度随访一次(第4阶段:确诊感染),直至开始抗逆转录病毒治疗(ART)(第5阶段)。在HIV疾病进展的每个阶段重复测量CD4计数和46个协变量。应用多级偏最小二乘法作为变量约简技术来确定最有力的CD4计数协变量。
46个研究的临床属性中只有18个是最有力的CD4计数协变量,前8个与CD4计数呈正相关且独立相关。除了确认的淋巴细胞外,这些协变量还有嗜碱性粒细胞、白蛋白、血细胞比容、碱性磷酸酶(ALP)、平均红细胞体积(MCV)、血小板、钾和单核细胞。总体而言,电解质、蛋白质和红细胞是最有力协变量的主要类别。
许多先前建议的持续CD4计数临床协变量中只有少数显示出有可能成为治疗过程的重要组成部分。通过有效纳入和管理协变量以长期影响CD4细胞反应来延长HIV疾病进展的预处理期,有可能延迟与ART副作用相关的挑战。