Nakajima Toshiaki, Ohtani Hitoshi, Naruse Taeko, Shibata Hiroki, Mimaya Jun-Ich, Terunuma Hiroshi, Kimura Akinori
Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 101-0062, Japan.
Immunogenetics. 2007 Oct;59(10):793-8. doi: 10.1007/s00251-007-0252-4. Epub 2007 Sep 14.
We set up a cohort of HIV-infected, asymptomatic Japanese patients with hemophilia for follow-up study in 1995. All subjects who had been infected with HIV-1 for more than 10 years met the criteria for long-term nonprogressors (LTNPs) at the time of entry; however, some of them later developed lymphopenia and required antiretroviral treatment during five more years of observation. In this study, we investigated the impacts of the CCL3L1 dose on the long-term prognosis in the subjects with chronic HIV-1 infection. We collected genomic DNA from 95 long-term survivors including 48 nonprogressors and 47 subjects receiving antiretroviral treatment. The distributions of CCL3L1 copy number significantly differed between the 95 HIV-1-infected subjects with hemophilia and 205 controls. Average copy number of CCL3L1 in the HIV-1-infected subjects was significantly lower than in control (5.00 +/- 0.22 vs 3.35 +/- 0.24, p < 0.001). Moreover, the subjects possessing two or less copies of CCL3L1 had significantly higher risk of acquiring HIV-1. However, CCL3L1 copy number variations had no significant effect on the disease progression among the LTNP subjects who had been afflicted with chronic HIV-1 infection for more than 15 years, when compared between nonprogressors and patients under treatment (3.68 +/- 0.37 vs 3.02 +/- 0.29, ns). Furthermore, variations in the CCL3L1 copy number had little effect on the levels of HIV-1 load among them. We conclude that variation in the CCL3L1 copy number is apparently not a factor that determines the prognosis of chronic HIV-1 infection, even though it is linked to HIV-1 susceptibility.
1995年，我们建立了一个对感染HIV的无症状日本血友病患者队列进行随访研究。所有感染HIV-1超过10年的受试者在入组时均符合长期不进展者（LTNPs）的标准；然而，其中一些人后来出现淋巴细胞减少，并在接下来的五年观察期内需要接受抗逆转录病毒治疗。在本研究中，我们调查了CCL3L1剂量对慢性HIV-1感染受试者长期预后的影响。我们从95名长期存活者中收集了基因组DNA，其中包括48名不进展者和47名接受抗逆转录病毒治疗的受试者。95名感染HIV-1的血友病受试者与205名对照者之间CCL3L1拷贝数的分布存在显著差异。HIV-1感染受试者中CCL3L1的平均拷贝数显著低于对照组（5.00±0.22对3.35±0.24，p<0.001）。此外，CCL3L1拷贝数为两个或更少的受试者感染HIV-1的风险显著更高。然而，当比较不进展者和接受治疗的患者时，CCL3L1拷贝数变异对慢性HIV-1感染超过15年的LTNP受试者的疾病进展没有显著影响（3.68±0.37对3.02±0.29，无显著性差异）。此外，CCL3L1拷贝数变异对他们体内HIV-1载量水平的影响很小。我们得出结论，CCL3L1拷贝数变异显然不是决定慢性HIV-1感染预后的因素，尽管它与HIV-1易感性有关。
