Lower CD4+ T lymphocyte nadirs may indicate limited immune reconstitution in HIV-1 infected individuals on potent antiretroviral therapy: Analysis of immunophenotypic marker results of AACTG 5067
Lower CD4+ T lymphocyte nadirs may indicate limited immune reconstitution in HIV-1 infected individuals on potent antiretroviral therapy: Analysis of immunophenotypic marker results of AACTG 5067
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DOI：
10.1007/s10875-005-2816-0
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发表时间：
2005-03-01
影响因子：
9.1
通讯作者：
Jacobson, MA
中科院分区：
文献类型：
--
作者：
D'Amico, R;Yang, YJ;Jacobson, MA
背景：尽管开始强效抗逆转录病毒治疗（ART）可以显著改善艾滋病患者的免疫紊乱，但尚不清楚哪些因素在决定免疫重建程度方面最重要。方法：在基线和第12周对6组受试者（n = 81）进行全血分析：急性或继发免疫重建的吉罗氏肺囊虫（以前称为卡氏肺囊虫）肺炎（PcP）（两组）和巨细胞病毒（CMV）视网膜炎（两组），未感染艾滋病的hiv（一组）和健康志愿者（一组）。计数绝对CD4+和CD8+ T淋巴细胞、幼稚（CD45RA+）和记忆（CD45RO+） CD4+ T淋巴细胞、活化CD8+ T淋巴细胞（CD8+/CD38+/HLA-DR）百分比、CD4+和CD8+ T淋巴细胞上CD28的表达。结果：重组CMV组CD4+ T淋巴细胞最低点低于重组PcP组(15个细胞/mm(3) vs 48个细胞/mm(3))；p = 0.013)，与重组PcP组相比，绝对CD4+、CD8+和初始CD4+ T淋巴细胞明显降低，记忆CD4+ T淋巴细胞有降低的趋势。此外，重组组之间未检测到HIV-1 RNA的受试者比例没有差异。重组组患者CD4+、记忆CD4+和初始CD4+ T淋巴细胞的绝对水平明显低于hiv阳性对照组，CD8+ T淋巴细胞的活化率明显高于hiv阴性对照组，CD8+CD28表达率明显低于hiv阴性对照组。结论：CD4+ T淋巴细胞最低点与hiv感染者免疫重建程度的关联表明，尽管抗逆转录病毒治疗有效，HIV-1仍可能造成不可修复的免疫系统损伤。
Background: Although initiation of potent antiretroviral therapy (ART) has significantly improved immune perturbations in individuals with AIDS, it is unclear which factors are most important in determining the degree of immune reconstitution.Methods: Whole blood was analyzed at baseline and week 12 in six groups of subjects (n = 81): those with acute or following immune reconstitution after Pneumocystis jirovecii (previously known as Pneumocystis carinii) pneumonia (PcP) (two groups) and cytomegalovirus (CMV) retinitis (two groups), HIV-infection without AIDS (one group), and healthy volunteers (one group). Absolute CD4+ and CD8+ T lymphocytes, naive (CD45RA+) and memory (CD45RO+) CD4+ T lymphocytes and percentages of activated CD8+ T lymphocytes (CD8+/CD38+/HLA-DR), and CD28 expression on CD4+ and CD8+ T lymphocytes were enumerated.Results: The reconstituted CMV group, which had a history of a lower CD4+ T lymphocyte nadir compared to the reconstituted PcP group (15 cells/mm(3) versus 48 cells/mm(3); p = .013), had significantly lower absolute CD4+, CD8+ and naive CD4+ T lymphocytes and a trend toward lower memory CD4+ T lymphocytes compared to the reconstituted PcP group. Moreover, no difference was noted between the reconstituted groups in the proportion of subjects with undetected HIV-1 RNA. The reconstituted subjects had significantly lower absolute CD4+, memory CD4+ and naive CD4+ T lymphocytes than the HIV-positive controls and a significantly higher percentage of activated CD8+ T lymphocytes with a lower percentage of CD8+CD28 expression than the HIV-negative controls.Conclusion: The association of CD4+ T lymphocyte nadir with the extent of immune reconstitution in HIV-infected individuals suggests that HIV-1 may cause irreparable immune system damage despite potent ART.