Kumar D, Parato K, Kumar A, Sun E, Cameron D W, Angel J B
Department of Medicine, University of Ottawa, Ontario, Canada.
AIDS Res Hum Retroviruses. 1999 Aug 10;15(12):1073-7. doi: 10.1089/088922299310368.
The chemokine receptor CCR5 has been shown to be a major coreceptor for HIV-1. The chemokines that bind to this receptor (MIP-1alpha, MIP-1beta, and RANTES) are potent inhibitors of HIV replication and may play an important role in the pathophysiology of HIV disease. We investigated the effect of potent antiretroviral therapy (ritonavir and saquinavir) on the production of MIP-1alpha, MIP-1beta, and RANTES in 19 HIV-infected patients who had sustained decreases in plasma HIV RNA levels (<200 copies/ml). Chemokine concentrations were measured in serum, plasma, and PHA-stimulated PBMCs at baseline and 24 and 48 weeks after initiating therapy. MIP-1alpha, MIP-1beta, and RANTES levels in serum and plasma did not significantly change in the 48-week period. In contrast, MIP-1alpha and MIP-1beta secreted by PHA-stimulated PBMCs increased at 24 weeks, with this increase sustained at 48 weeks, whereas no significant change was observed in PHA-induced RANTES production. A significant positive correlation was found between the changes in PHA-induced chemokine production and baseline CD4+ T cell counts. These data demonstrate that sustained suppression of viral replication by potent antiretroviral therapy has a potentially beneficial effect on chemokine production and early initiation of this therapy appears to confer a more favorable chemokine profile.
趋化因子受体CCR5已被证明是HIV-1的主要共受体。与该受体结合的趋化因子(MIP-1α、MIP-1β和RANTES)是HIV复制的有效抑制剂,可能在HIV疾病的病理生理学中起重要作用。我们研究了强效抗逆转录病毒疗法(利托那韦和沙奎那韦)对19例血浆HIV RNA水平持续下降(<200拷贝/ml)的HIV感染患者中MIP-1α、MIP-1β和RANTES产生的影响。在基线以及开始治疗后24周和48周时,测量血清、血浆和PHA刺激的外周血单核细胞中的趋化因子浓度。在48周期间,血清和血浆中的MIP-1α、MIP-1β和RANTES水平没有显著变化。相比之下,PHA刺激的外周血单核细胞分泌的MIP-1α和MIP-1β在24周时增加,并在48周时持续增加,而PHA诱导的RANTES产生没有观察到显著变化。PHA诱导的趋化因子产生变化与基线CD4 + T细胞计数之间存在显著正相关。这些数据表明,强效抗逆转录病毒疗法持续抑制病毒复制对趋化因子产生具有潜在的有益作用,并且早期开始这种疗法似乎能带来更有利的趋化因子谱。