早期HIV感染期间的高效抗逆转录病毒疗法可逆转T细胞活化和成熟异常。瑞士HIV队列研究。

Highly active antiretroviral therapy during early HIV infection reverses T-cell activation and maturation abnormalities. Swiss HIV Cohort Study.

作者信息

Bisset L R, Cone R W, Huber W, Battegay M, Vernazza P L, Weber R, Grob P J, Opravil M

机构信息

Department of Internal Medicine, University Hospital, Zürich, Switzerland.

出版信息

AIDS. 1998 Nov 12;12(16):2115-23. doi: 10.1097/00002030-199816000-00006.

DOI:10.1097/00002030-199816000-00006

PMID:9833852

Abstract

OBJECTIVES

To evaluate the impact of early initiation of highly active antiretroviral therapy (HAART) on disease-induced T-cell activation and maturation abnormalities during asymptomatic HIV infection.

DESIGN

A prospective open-label trial of zidovudine, lamivudine and ritonavir in treatment-naive asymptomatic HIV-infected individuals with CD4 cells > or = 400 x 10(6)/l.

METHODS

Peripheral blood CD4+ and CD8+ T cells derived from 15 asymptomatic HIV-infected individuals (median baseline CD4+ cells, 608 x 10(6)/l; CD8+ cells, 894 x 10(6)/l; plasma HIV RNA, 3.93 log10 copies/ml) undergoing therapy with zidovudine (300 mg twice daily), lamivudine (150 mg twice daily), and ritonavir (600 mg twice daily) were assessed for changes in expression of phenotypic markers of T-cell activation (HLA-DR and CD38) and maturation (CD45RA and CD45RO). At weeks 0, 2, 4, 8, 12, 16, 20 and 24, T-cell subsets were quantified by flow cytometry and plasma HIV viral loads determined using reverse transcription PCR.

RESULTS

HAART-induced decrease in plasma HIV RNA levels coincided with a significant reduction in numbers of activated CD4+/HLA-DR+ (maximum change, -36%; P < or = 0.05), CD8+/HLA-DR+ (maximum change, -66%; P < or = 0.005) and CD8+/CD38+ (maximum change, -51%; P < or = 0.01) T cells. A concomitant significant increase in numbers of naive CD4+/CD45RA+ (maximum change, +12%; P < or = 0.005) and memory CD4+/CD45RO+ (maximum change, +6%; P < or = 0.05) T cells was also evident, which contrasted with a significant decrease in memory CD8+/CD45RO+ cells (maximum change, -42%; P < or = 0.005).

CONCLUSION

The observed ability of HAART during early asymptomatic HIV infection to initiate rapid reversal of disease-induced T-cell activation and maturation abnormalities, while preserving pretherapy levels of immune function, supports the concept that therapeutic advantage is to be gained by commencing early aggressive antiretroviral therapy.

摘要

目的

评估早期开始高效抗逆转录病毒治疗（HAART）对无症状HIV感染期间疾病诱导的T细胞活化和成熟异常的影响。

设计

一项针对未接受过治疗的无症状HIV感染者（CD4细胞≥400×10⁶/l）使用齐多夫定、拉米夫定和利托那韦的前瞻性开放标签试验。

方法

对15名无症状HIV感染者（基线CD4⁺细胞中位数为608×10⁶/l；CD8⁺细胞为894×10⁶/l；血浆HIV RNA为3.93 log₁₀拷贝/ml）进行齐多夫定（每日两次，每次300 mg）、拉米夫定（每日两次，每次150 mg）和利托那韦（每日两次，每次600 mg）治疗，评估其外周血CD4⁺和CD8⁺ T细胞中T细胞活化（HLA-DR和CD38）和成熟（CD45RA和CD45RO）表型标志物表达的变化。在第0、2、4、8、12、16、20和24周，通过流式细胞术对T细胞亚群进行定量，并使用逆转录PCR测定血浆HIV病毒载量。

结果

HAART导致血浆HIV RNA水平下降，同时活化的CD4⁺/HLA-DR⁺ T细胞数量显著减少（最大变化为-36%；P≤0.05）、CD8⁺/HLA-DR⁺ T细胞数量显著减少（最大变化为-66%；P≤0.005）以及CD8⁺/CD38⁺ T细胞数量显著减少（最大变化为-51%；P≤0.01）。同时，幼稚CD4⁺/CD45RA⁺ T细胞数量显著增加（最大变化为+12%；P≤0.005）以及记忆CD4⁺/CD45RO⁺ T细胞数量显著增加（最大变化为+6%；P≤0.05）也很明显，这与记忆CD8⁺/CD45RO⁺细胞数量显著减少形成对比（最大变化为-42%；P≤0.005）。