HIV-neutralizing immunoglobulin A and HIV-specific proliferation are independently associated with reduced HIV acquisition in Kenyan sex workers

HIV-neutralizing immunoglobulin A and HIV-specific proliferation are independently associated with reduced HIV acquisition in Kenyan sex workers
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DOI:
10.1097/qad.0b013e3282f56b64
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发表时间:
2008-03-30
期刊:
影响因子:
3.8
通讯作者:
Broliden, Kristina
Broliden, Kristina
中科院分区:
医学2区
文献类型:
--
作者:
Hirbod, Taha;Kaul, Rupert;Broliden, Kristina

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目的:HIV中和免疫球蛋白A(伊加)和HIV特异性细胞免疫在高度暴露、持续血清阴性(HEPS)个体中已有描述,但尚未进行良好对照研究。我们进行了一项前瞻性,巢式病例对照研究,以探讨生殖器伊加和系统性细胞免疫反应与随后的艾滋病毒收购在高风险的肯尼亚女性性工作者(FSWs)的关联设计和方法:每月抗生素预防性传播疾病/艾滋病毒感染的随机试验,以防止性传播疾病/艾滋病毒感染,从1998年至2002年在艾滋病毒未感染的肯尼亚FSWs。试验完成后,根据研究组、HIV血清阴性随访持续时间和队列入组时间,将获得HIV的FSW(病例)与持续未感染的对照组按1:4匹配。设盲的调查人员分析的能力,在注册的生殖器伊加中和主要的HIV分离株,以及系统的HIV特异性细胞IFN γ-修饰的酶联免疫斑点和增殖respons.Results:研究队列包括113 FSW:24例获得艾滋病毒和89匹配的对照。生殖器HIV中和伊加与HIV感染减少相关(P= 0.003),HIV特异性增殖也是如此(P= 0.002),这些相关性是累加的。HIV特异性IFN γ的产生在病例组和对照组之间没有差异。在多变量分析中,HIV中和伊加和HIV特异性增殖各自独立地与缺乏HIV获得相关。生殖器疱疹(HSV 2)与HIV风险增加和减少检测HIV中和伊加。结论:生殖器HIV中和伊加和系统HIV特异性增殖反应,由盲法调查分析,前瞻性与HIV nonacquisition。这些免疫反应的诱导可能是HIV疫苗的重要目标。(C)2008年威科健康|利平科特威廉姆斯&威尔金斯。
Objectives: HIV-neutralizing immunoglobulin A (IgA) and HIV-specific cellular immunity have been described in highly exposed, persistently seronegative (HEPS) individuals, but well controlled studies have not been performed. We performed a prospective, nested case-control study to examine the association of genital IgA and systemic cellular immune responses with subsequent HIV acquisition in high-risk Kenyan female sex workers (FSWs).Design and methods: A randomized trial of monthly antibiotic prophylaxis to prevent sexually transmitted disease/HIV infection was performed from 1998 to 2002 in HIV-uninfected Kenyan FSWs. After the completion of trial, FSWs who had acquired HIV (cases) were matched 1 : 4 with persistently uninfected controls based on study arm, duration of HIV-seronegative follow-up, and time of cohort enrolment. Blinded investigators assayed the ability at enrolment of genital IgA to neutralize primary HIV isolates as well as systemic HIV-specific cellular IFN gamma-modified enzyme-linked immunospot and proliferative responses.Results: The study cohort comprised 113 FSWs: 24 cases who acquired HIV and 89 matched controls. Genital HIV-neutralizing IgA was associated with reduced HIV acquisition (P= 0.003), as was HIV-specific proliferation (P= 0.002), and these associations were additive. HIV-specific IFN gamma production did not differ between case and control groups. In multivariable analysis, HIV-neutralizing IgA and HIV-specific proliferation each remained independently associated with lack of HIV acquisition. Genital herpes (HSV2) was associated with increased HIV risk and with reduced detection of HIV-neutralizing IgA.Conclusion: Genital HIV-neutralizing IgA and systemic HIV-specific proliferative responses, assayed by blinded investigators, were prospectively associated with HIV nonacquisition. The induction of these immune responses may be an important goal for HIV vaccines. (C) 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins.