3rd Internal Medicine Department-Infectious Diseases Unit, Red Cross General Hospital, Athens, Greece.
Int J Immunopathol Pharmacol. 2012 Jan-Mar;25(1):247-58. doi: 10.1177/039463201202500127.
Human Immunodeficiency Virus (HIV)-infected patients are at increased risk for cardiovascular diseases partly due to chronic inflammation. Some antiretroviral drugs and Highly Active Anti-Retroviral Therapy (HAART) regimens seem to be related and amplify this increased risk, especially the ones containing abacavir. Platelet-Activating-Factor (PAF) is a potent inflammatory mediator that is implicated in both cardiovascular diseases and HIV-related manifestations. Our objective is to study the in vivo effect of the abacavir/lamivudine/efavirenz first-line HAART regimen on PAF metabolism in HIV-infected patients. The specific activities of PAF basic biosynthetic enzymes in leukocytes and platelets, PAF-cholinephosphotransferase (PAF-CPT) and lyso-PAF-acetyltransferase (Lyso-PAF-AT), but also those of PAF-basic catabolic enzymes, PAF acetylhydrolase (PAF-AH) in leukocytes and platelets and Lipoprotein-associated-Phospholipase-A2 (LpPLA2) in plasma, were measured in blood samples of 10 asymptomatic naïve male HIV-infected patients just before and after 1, 3 and 6 months of treatment. CD4 cell counts, viral load and several biochemical markers were also measured in the same blood samples of these patients. The repeated ANOVA measures and the Pearson r criterion were used for studying statistical differences and correlations - partial correlations respectively. Even though viral load was decreased and CD4 cell counts were beneficially increased after treatment with the abacavir/lamivudine/efavirenz regimen, the main enzyme of the remodelling PAF-synthesis that is implicated in pro-atherogenic inflammatory procedures, Lyso-PAF-AT activity, was increased at 3 months of treatment in both leukocytes and platelets, while the main enzyme of PAF-degradation, PAF-AH, was increased as a response only in leukocytes at the 3rd month. Although the abacavir/lamivudine/efavirenz HAART regimen exhibits very efficient antiretroviral activities, on the other hand it induces an in vivo transient increase in the inflammation-related remodeling PAF-biosynthetic pathway. This finding supports the hypothesis of inflammation-mediated increased cardiovascular risk in HIV-infected patients during the first months of abacavir-containing HAART.
人类免疫缺陷病毒（HIV）感染患者发生心血管疾病的风险增加，部分原因是慢性炎症。一些抗逆转录病毒药物和高效抗逆转录病毒疗法（HAART）方案似乎与这种风险增加有关，并使其加剧，尤其是包含阿巴卡韦的方案。血小板激活因子（PAF）是一种强效的炎症介质，与心血管疾病和 HIV 相关表现均有关联。我们的目的是研究阿巴卡韦/拉米夫定/依非韦伦一线 HAART 方案对 HIV 感染患者体内 PAF 代谢的影响。白细胞和血小板中 PAF 基本生物合成酶（PAF 碱性磷酸酶、PAF-胆碱磷酸转移酶（PAF-CPT）和溶酶体-PAF-乙酰转移酶（Lyso-PAF-AT））、白细胞和血小板中 PAF 碱性代谢酶（PAF 乙酰水解酶（PAF-AH））以及血浆中脂蛋白相关磷脂酶 A2（LpPLA2）的特异性活性，在 10 名无症状的初治男性 HIV 感染患者治疗前、治疗 1、3 和 6 个月后，分别在血液样本中进行了测量。在这些患者的相同血液样本中还测量了 CD4 细胞计数、病毒载量和几种生化标志物。采用重复方差分析和 Pearson r 标准，分别用于研究统计差异和相关性——偏相关。尽管阿巴卡韦/拉米夫定/依非韦伦方案治疗后病毒载量降低，CD4 细胞计数升高，但与动脉粥样硬化前炎症过程中涉及的促动脉粥样硬化炎症相关的 PAF 合成的主要酶（溶酶体-PAF-AT 活性）在治疗 3 个月时在白细胞和血小板中均增加，而 PAF 降解的主要酶（PAF-AH）仅在第 3 个月时白细胞中增加。尽管阿巴卡韦/拉米夫定/依非韦伦 HAART 方案具有非常有效的抗逆转录病毒活性，但另一方面，它会导致体内与炎症相关的 PAF 生物合成途径在最初几个月内短暂增加。这一发现支持了在阿巴卡韦包含的 HAART 治疗的最初几个月中，HIV 感染患者的炎症介导的心血管风险增加的假设。
