Scadden D T, Pickus O, Hammer S M, Stretcher B, Bresnahan J, Gere J, McGrath J, Agosti J M
Division of Hematology/Oncology, New England Deaconess Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
AIDS Res Hum Retroviruses. 1996 Aug 10;12(12):1151-9. doi: 10.1089/aid.1996.12.1151.
Neutropenia complicates HIV disease or its treatment in a large proportion of patients. Hematopoietic growth factor support has been tested in a number of clinical settings in HIV disease and has been demonstrated to be of benefit for specific parameters. One consideration regarding the use of hematopoietic growth factors in HIV disease is their potential effect on HIV viral burden, since alterations in HIV expression have been documented with certain cytokines in vitro. It has also been reported that some cytokines, notably GM-CSF, potentiate the antiviral properties of thymidine analogs such as zidovudine (AZT) in vitro. We tested these observations in vivo. Twelve HIV-positive patients with a CD4 cell count < or = 200/mm3 or HIV plasma viremia who were receiving a stable dose of zidovudine were enrolled into three dose cohorts of yeast-derived GM-CSF at 50, 125, or 250 micrograms/m2 daily by subcutaneous self-injection for 28 days. Measurements of HIV activity included serum acid-dissociated HIV p24 antigen levels, plasma and peripheral blood mononuclear cell (PBMC) limiting dilution HIV culture, and plasma HIV quantitative competitive polymerase chain reaction (PCR). Serum and intracellular zidovudine levels were measured as well as hematologic, immunologic, and toxicity parameters. Virologic measures showed neither significant upregulation nor downregulation of serum acid-dissociated HIV p24 antigen, plasma and PBMC HIV culture, or PCR in association with GM-CSF administration. A trend toward increased intracellular AZT levels was noted, but this did not achieve statistical significance (p = 0.073). CD4 and CD8 lymphocytes were essentially unaffected while absolute neutrophil counts increased with GM-CSF administration as expected. These data suggest that administration of GM-CSF does not perturb HIV activity or immunologic parameters in patients receiving AZT for advanced HIV disease. No potentiation of AZT antiviral effect was demonstrated.
中性粒细胞减少在很大一部分艾滋病患者中会使病情或其治疗变得复杂。造血生长因子支持疗法已在艾滋病的多种临床环境中进行了测试，并已证明对特定指标有益。在艾滋病中使用造血生长因子的一个考虑因素是它们对艾滋病毒病毒载量的潜在影响，因为在体外已记录到某些细胞因子会改变艾滋病毒的表达。也有报道称，一些细胞因子，尤其是粒细胞-巨噬细胞集落刺激因子（GM-CSF），在体外可增强核苷类似物如齐多夫定（AZT）的抗病毒特性。我们在体内对这些观察结果进行了测试。12名CD4细胞计数≤200/mm³或有艾滋病毒血浆病毒血症且正在接受稳定剂量齐多夫定治疗的艾滋病毒阳性患者，被纳入三个剂量组，通过皮下自我注射，每天接受50、125或250微克/平方米的酵母衍生GM-CSF，持续28天。艾滋病毒活性的测量包括血清酸解离艾滋病毒p24抗原水平、血浆和外周血单个核细胞（PBMC）极限稀释艾滋病毒培养以及血浆艾滋病毒定量竞争聚合酶链反应（PCR）。同时测量了血清和细胞内齐多夫定水平以及血液学、免疫学和毒性参数。病毒学检测显示，与GM-CSF给药相关的血清酸解离艾滋病毒p24抗原、血浆和PBMC艾滋病毒培养或PCR均未出现显著上调或下调。细胞内AZT水平有升高趋势，但未达到统计学意义（p = 0.073）。CD4和CD8淋巴细胞基本未受影响，而绝对中性粒细胞计数如预期随着GM-CSF给药而增加。这些数据表明，对于晚期艾滋病患者，在接受AZT治疗时给予GM-CSF不会干扰艾滋病毒活性或免疫参数。未证明AZT的抗病毒作用有增强。
