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

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
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DOI:
10.1097/qad.0b013e328182df03
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发表时间:
2007-06-19
期刊:
影响因子:
3.8
通讯作者:
Brander, Christian
Brander, Christian
中科院分区:
医学2区
文献类型:
--
作者:
Bihl, Florian;Mosam, Anisa;Brander, Christian

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背景:卡波西肉瘤相关疱疹病毒(KSHV)在南非流行,艾滋病相关性卡波西肉瘤(KS)的临床表现是一个重要的临床问题。虽然HAART在KS消退中的积极作用已经得到了很好的证实,但关于疱疹病毒特异性细胞免疫在疾病改善中的作用还知之甚少。设计:33名未接受治疗的HIV C分支感染KS的患者被随机分配到两个治疗组(HAART+全身化疗和HAART单独治疗)。方法:采用干扰素-γ酶联免疫斑点法检测治疗前和治疗后11个月的KSHV、Epstein-Barr病毒和HIV特异性细胞免疫。实时聚合酶链式反应检测细胞相关性KSHV病毒血症。结果:随着时间的推移,随着时间的推移,CD4细胞计数的强劲增加和HIV病毒载量的抑制与KSHV特异性细胞免疫反应的显著增加平行。虽然在5个月后缓慢增加,但KSHV特异性T细胞应答仅在I-I个月后显著升高,裂解抗原和潜伏抗原都是更常见的靶标。与单用HAART相比,HAART加化疗有改善临床结果的趋势,并且在HAART加化疗的受试者中伴随着细胞KSHV病毒载量的显著下降,而单用HAART的受试者在治疗11个月后并未出现KSHV病毒载量。结论:数据显示KS的临床改善与KSHV特异性细胞免疫的重新出现之间存在时间相关性,并表明联合治疗有效地抑制了KSHV病毒的复制。(C)V 2007 Lippincott Williams&Wilkins。
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 I I 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.(C)V 2007 Lippincott Williams & Wilkins.