卡波西肉瘤相关疱疹病毒特异性免疫重建以及高效抗逆转录病毒治疗/化疗联合方案对感染C型HIV且患有卡波西肉瘤个体的抗病毒作用

Kaposi's sarcoma-associated herpesvirus-specific immune reconstitution and antiviral effect of combined HAART/chemotherapy in HIV clade C-infected individuals with Kaposi's sarcoma.

作者信息

Bihl Florian, Mosam Anisa, Henry Leah N, Chisholm John V, Dollard Sheila, Gumbi Pamela, Cassol Edana, Page Taryn, Mueller Nicolas, Kiepiela Photini, Martin Jeff N, Coovadia Hoosen M, Scadden David T, Brander Christian

机构信息

Partners AIDS Research Center, Massachusetts General Hospital and Harvard Medical School, 13th Street, Charlestown, MA 02129, USA.

出版信息

AIDS. 2007 Jun 19;21(10):1245-52. doi: 10.1097/QAD.0b013e328182df03.

DOI:10.1097/QAD.0b013e328182df03

PMID:17545700

Abstract

BACKGROUND

Kaposi's sarcoma-associated herpesvirus (KSHV) is endemic in South Africa and the clinical manifestation of AIDS-associated Kaposi's sarcoma (KS) represents a significant clinical problem. Whereas the positive effects of HAART on the regression of KS have been well established, less is known about the role of herpesvirus-specific cellular immunity in disease improvement.

DESIGN

Thirty-three treatment-naive HIV clade C-infected individuals with KS were randomly assigned into two treatment arms (HAART plus systemic chemotherapy versus HAART alone). KSHV-specific cellular immune responses, viral loads and clinical outcome were evaluated.

METHODS

KSHV, Epstein-Barr virus and HIV-specific cellular immunity was measured using an IFN-gamma enzyme-linked immunospot assay in samples obtained at baseline and up to 11 months after treatment initiation. Cell-associated KSHV viremia was determined by real-time polymerase chain reaction.

RESULTS

Robust increases in CD4 cell counts and suppressed HIV viral loads were seen in parallel with significant increases in the KSHV-specific cellular immune responses over time. Although slowly increasing after 5 months, KSHV-specific T-cell responses were significantly elevated only after 11 months, with both lytic and latent antigens being more frequently targeted. A trend towards better clinical outcome with HAART plus chemotherapy treatment was observed compared with HAART alone, and was accompanied by a significant reduction in cellular KSHV viral load in the HAART plus chemotherapy-treated subjects but not those treated with HAART alone after 11 months of treatment.

CONCLUSION

The data show a temporal association between the clinical improvement of KS and the re-appearance of KSHV-specific cellular immunity, and demonstrate an effective suppression of KSHV viral replication using combination therapy.

摘要

背景

卡波西肉瘤相关疱疹病毒（KSHV）在南非呈地方性流行，艾滋病相关卡波西肉瘤（KS）的临床表现是一个重大的临床问题。虽然高效抗逆转录病毒治疗（HAART）对KS消退的积极作用已得到充分证实，但关于疱疹病毒特异性细胞免疫在疾病改善中的作用知之甚少。

设计

33例初治的HIV C亚型感染且患有KS的个体被随机分为两个治疗组（HAART加全身化疗与单纯HAART）。评估了KSHV特异性细胞免疫反应、病毒载量和临床结局。

方法

使用γ干扰素酶联免疫斑点试验，在基线时以及治疗开始后长达11个月采集的样本中，检测KSHV、爱泼斯坦-巴尔病毒和HIV特异性细胞免疫。通过实时聚合酶链反应测定细胞相关的KSHV病毒血症。

结果

随着时间的推移，CD4细胞计数显著增加且HIV病毒载量受到抑制，同时KSHV特异性细胞免疫反应也显著增强。虽然在5个月后缓慢增加，但KSHV特异性T细胞反应仅在11个月后才显著升高，裂解抗原和潜伏抗原都更频繁地成为靶点。与单纯HAART相比，观察到HAART加化疗治疗有更好临床结局的趋势，并且在治疗11个月后，接受HAART加化疗治疗的受试者细胞KSHV病毒载量显著降低，而单纯接受HAART治疗的受试者则没有。