Bisset L R, Rothen M, Joller-Jemelka H I, Dubs R W, Grob P J, Opravil M
Division of Clinical Immunology, University Hospital, Zürich, Switzerland.
AIDS. 1997 Mar 15;11(4):485-91. doi: 10.1097/00002030-199704000-00012.
To evaluate the in vivo relationship between HIV replication and circulating levels of the chemokines macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, RANTES (acronym for Regulated upon Activation, Normal T-cell Expressed and presumably Secreted), interleukin (IL)-16 and monocyte chemotactic protein (MCP)-1, which have recently been characterized as factors capable of regulating in vitro HIV replication.
We have compared changes in plasma HIV-RNA levels and circulating levels of MIP-1 alpha, MIP-1 beta, RANTES, IL-16 and MCP-1 in 20 severely immunodeficient HIV-infected individuals (CD4+ T cells = 14 +/- 3 cells x 10(6)/l; plasma HIV RNA = 4.45 +/- 0.27 log 10 copies/ml) undergoing treatment with the HIV protease inhibitor indinavir that added to pre-existing nucleoside-based therapy. At weeks 0, 2, 6 and 12, viral load was quantified using a commercial reverse-transcription polymerase chain reaction assay, peripheral blood T-cell subpopulations assessed by flow cytometry, and chemokine levels quantified using commercial sandwich enzyme-linked immunosorbent assay kits.
Following initiation of indinavir-based therapy, significant decreases in plasma HIV-RNA levels (change = 2.0 +/- 0.75 log 10 copies/ml) were observed in conjunction with significant increases in absolute CD4+ (change = 83 +/- 19 cells x 10(6)/l) and CD8+ (change = 293 +/- 96 cells x 10(6)/l) T-cell numbers. Concomitantly, significant increases in MIP-1 alpha (19% increase), MIP-1 beta (14% increase), RANTES (15% increase) and IL-16 (1213% increase) levels occurred. In contrast, MCP-1 levels decreased significantly (47% decrease).
The in vivo demonstration of an association between diminishing plasma HIV-RNA levels and the emergence of a circulating chemokine profile capable of inhibiting HIV replication corroborates recent in vitro observations and provides evidence for the restoration of chemokine capacity by HIV protease inhibitor-based therapy.
评估人类免疫缺陷病毒（HIV）复制与趋化因子巨噬细胞炎性蛋白（MIP）-1α、MIP-1β、调节激活正常T细胞表达和分泌因子（RANTES）、白细胞介素（IL）-16及单核细胞趋化蛋白（MCP）-1循环水平之间的体内关系，这些趋化因子最近被确定为能够在体外调节HIV复制的因子。
我们比较了20名严重免疫缺陷的HIV感染个体（CD4+T细胞=14±3×10⁶/升；血浆HIV RNA=4.45±0.27 log₁₀拷贝/毫升）在接受添加到已有核苷类疗法中的HIV蛋白酶抑制剂茚地那韦治疗时，血浆HIV-RNA水平以及MIP-1α、MIP-1β、RANTES、IL-16和MCP-1循环水平的变化。在第0、2、6和12周，使用商业逆转录聚合酶链反应测定法定量病毒载量，通过流式细胞术评估外周血T细胞亚群，并使用商业夹心酶联免疫吸附测定试剂盒定量趋化因子水平。
在开始基于茚地那韦的治疗后，观察到血浆HIV-RNA水平显著下降（变化=2.0±0.75 log₁₀拷贝/毫升），同时绝对CD4+（变化=83±19×10⁶/升）和CD8+（变化=293±96×10⁶/升）T细胞数量显著增加。同时，MIP-1α水平显著增加（增加19%）；MIP-1β水平显著增加（增加14%）；RANTES水平显著增加（增加15%）；IL-16水平显著增加（增加1213%）。相比之下，MCP-1水平显著下降（下降47%）。
血浆HIV-RNA水平降低与能够抑制HIV复制的循环趋化因子谱出现之间存在关联的体内证据，证实了最近的体外观察结果，并为基于HIV蛋白酶抑制剂的疗法恢复趋化因子能力提供了证据。
