Impaired hepatitis C virus-specific T cell responses and recurrent hepatitis C virus in HIV coinfection.
Impaired hepatitis C virus-specific T cell responses and recurrent hepatitis C virus in HIV coinfection.
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DOI：
10.1371/journal.pmed.0030492
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发表时间：
2006-12
期刊：
影响因子：
15.8
通讯作者：
Walker, Bruce D.
中科院分区：
文献类型：
--
作者：
Kim, Arthur Y.;Wiesch, Julian Schulze zur;Kuntzen, Thomas;Timm, Joerg;Kaufmann, Daniel E.;Duncan, Jared E.;Jones, Andrea M.;Wurcel, Alysse G.;Davis, Benjamin T.;Gandhi, Rajesh T.;Robbins, Gregory K.;Allen, Todd M.;Chung, Raymond T.;Lauer, Georg M.;Walker, Bruce D.
丙型肝炎病毒（HCV）特异性T细胞反应对HCV病毒血症的自发解决至关重要。在这里，我们研究了嗜淋巴病毒HIV-1对合并感染患者维持HCV感染自发控制能力的影响。我们通过淋巴细胞增殖和干扰素γ ELISPOT检测了一大批有和没有HIV感染的hcv感染者的T细胞反应性。在47例HCV/HIV-1合并感染者中，与表现为慢性HCV病毒血症的合并感染者（7%,p = 0.016）相比，HCV自发控制与HCV特异性淋巴细胞增生性（LP）反应的发生率更高（35%），但与未感染HIV的HCV控制者相比，HCV自发控制与HCV特异性淋巴细胞增生性（LP）反应的发生率较低（86%,p = 0.003）。在合并感染的个体中，保留hcv特异性LP反应与较高的最低点CD4计数（r 2 = 0.45, p < 0.001）以及hcv特异性CD8+ T细胞干扰素-γ反应的存在和强度（p = 0.0014）相关。在长期随访中，25名合并感染的HCV控制者中有6人出现HCV病毒血症复发，而16名hiv -1阴性HCV控制者中0人出现HCV病毒血症复发（p = 0.03， log rank检验）。在这6例复发性HCV病毒血症患者中，复发后的HCV病毒血症程度与突破时的CD4计数呈负相关（r = - 0.94, p = 0.017）。这些结果表明，HIV感染削弱了对HCV的免疫反应——包括已清除HCV感染的人——并且自发控制HCV的HIV-1感染个体仍然具有HCV病毒血症第二次发作的显著风险。这些发现强调了在HIV-1合并感染的情况下，需要对HCV感染的明显控制者进行重复病毒RNA检测，并为在该人群中观察到的较高HCV持久性提供了可能的解释。HIV感染削弱了对HCV的免疫反应。即使已清除丙型肝炎病毒感染的个体仍有丙型肝炎病毒血症第二次发作的显著风险。由于共享传播途径（受污染的针头、受污染的血液制品，以及较小程度上无保护的性行为），很大比例的艾滋病毒感染者（估计范围在25%至33%之间）也感染了丙型肝炎病毒（HCV）。在大多数但不是所有的HCV感染者中，病毒感染是慢性的，会导致肝脏疾病，最终导致肝功能衰竭。疾病进展缓慢；感染者通常需要几十年的时间才能发展成严重的肝脏疾病。然而，在同时感染丙型肝炎病毒和艾滋病毒的人群中，丙型肝炎病毒引起的肝脏疾病往往出现得更快，进展也更快。由于高效抗逆转录病毒疗法（HAART）和机会性感染的预防延长了艾滋病毒感染者的寿命，丙型肝炎相关肝病已成为艾滋病毒感染者住院和死亡的主要原因。相当一部分感染丙型肝炎病毒的人设法控制了病毒，从未患上肝脏疾病，科学家们发现，这些人不知何故对丙型肝炎病毒产生了强烈的免疫反应。CD4+ T细胞，即被HIV感染和破坏的免疫细胞，在这种免疫反应中起着重要作用。本研究的目的是更好地了解HIV感染如何损害对HCV的特异性免疫反应，从而控制HCV疾病的进展。研究人员招募了四组患者，共94人，他们都感染了丙型肝炎病毒。两组患者同时感染艾滋病毒和丙型肝炎病毒，丙型肝炎病毒水平高或检测不到（每组30例）。另外两组包括未感染艾滋病毒的患者，要么HCV水平高，要么检测不到（每组17名患者）。研究人员关注的是那些尽管同时感染了艾滋病毒，但能够控制其丙型肝炎病毒感染的个体。他们发现，这些个体设法维持了相对较高的CD4+ T细胞水平，这些细胞专门识别HCV。然而，四分之一的患者（25人中有6人）在长达2.5年的整个观察期内未能将HCV水平保持在较低水平；他们血液中的HCV水平大幅上升，很可能是由于先前被抑制的病毒的复发（研究人员不能确定在再次接触受HCV污染的血液后没有患者再次感染，但没有证据表明他们有危险的行为）。复发患者血液中HCV水平的升高与CD4+ T细胞总数的下降同时发生。在这些个体复发后，HCV在研究期间没有恢复到不可检测的水平。在同一时期，16名未感染艾滋病毒但丙型肝炎病毒感染得到控制的人中没有一人复发可检测到的丙型肝炎病毒。尽管患者数量相对较少，但这些结果表明，HCV在初始控制病毒后更有可能在合并感染HIV的人群中复发，并且当CD4+ T细胞计数下降时，HCV控制就会丢失。这是对所有艾滋病毒阳性患者进行丙型肝炎合并感染检测的又一个原因。合并感染的患者，即使是那些似乎控制了HCV并且不会自动接受HCV治疗的患者，也应该定期检测HCV水平的升高。此外，将CD4+ T细胞维持在高水平可能对这些患者特别重要，这意味着医生可能会考虑比一般推荐的hiv感染者更早开始HAART治疗。然而，需要更多的研究来支持这些建议，特别是因为这项研究对患者的随访时间不够长，无法确定观察到的HCV失控的后果。请通过本摘要的在线版本http://dx.doi.org/10.1371/journal.pmed.0030492访问这些网站。艾滋病治疗数据网络关于HIV/HCV合并感染的情况说明书美国疾控中心关于HIV/HCV合并感染的情况说明书美国肝脏基金会，关于HIV和HCV MedlinePlus关于HCV页面的信息
Hepatitis C virus (HCV)-specific T cell responses are critical for spontaneous resolution of HCV viremia. Here we examined the effect of a lymphotropic virus, HIV-1, on the ability of coinfected patients to maintain spontaneous control of HCV infection. We measured T cell responsiveness by lymphoproliferation and interferon-γ ELISPOT in a large cohort of HCV-infected individuals with and without HIV infection. Among 47 HCV/HIV-1-coinfected individuals, spontaneous control of HCV was associated with more frequent HCV-specific lymphoproliferative (LP) responses (35%) compared to coinfected persons who exhibited chronic HCV viremia (7%, p = 0.016), but less frequent compared to HCV controllers who were not HIV infected (86%, p = 0.003). Preservation of HCV-specific LP responses in coinfected individuals was associated with a higher nadir CD4 count (r 2 = 0.45, p < 0.001) and the presence and magnitude of the HCV-specific CD8+ T cell interferon-γ response (p = 0.0014). During long-term follow-up, recurrence of HCV viremia occurred in six of 25 coinfected individuals with prior control of HCV, but in 0 of 16 HIV-1-negative HCV controllers (p = 0.03, log rank test). In these six individuals with recurrent HCV viremia, the magnitude of HCV viremia following recurrence inversely correlated with the CD4 count at time of breakthrough (r = −0.94, p = 0.017). These results indicate that HIV infection impairs the immune response to HCV—including in persons who have cleared HCV infection—and that HIV-1-infected individuals with spontaneous control of HCV remain at significant risk for a second episode of HCV viremia. These findings highlight the need for repeat viral RNA testing of apparent controllers of HCV infection in the setting of HIV-1 coinfection and provide a possible explanation for the higher rate of HCV persistence observed in this population. HIV infection impairs the immune response to HCV. Even individuals who have cleared HCV infection remain at significant risk for a second episode of HCV viremia. Because of shared transmission routes (contaminated needles, contaminated blood products, and, to a lesser extent, unprotected sex), a large proportion of HIV-infected individuals (estimates range between 25% and 33%) are also infected with the hepatitis C virus (HCV). In most but not all individuals infected with HCV, the virus infection is chronic and causes liver disease that can eventually lead to liver failure. Disease progress is slow; it often takes decades until infected individuals develop serious liver disease. In people infected with both HCV and HIV, however, liver disease caused by HCV often appears sooner and progresses faster. As highly active antiretroviral therapy (HAART) and prophylaxis of opportunistic infections increase the life span of persons living with HIV, HCV-related liver disease has become a major cause of hospital admissions and deaths among HIV-infected persons. A sizable minority of people who are infected with HCV manage to control the virus and never get liver disease, and scientists have found that these people somehow mounted a strong immune response against the hepatitis C virus. CD4+ T cells, the very immune cells that are infected and destroyed by HIV, play an important role in this immune response. The goal of the present study was to better understand how infection with HIV compromises the specific immune response to HCV and thereby the control of HCV disease progression. The researchers recruited four groups of patients, 94 in total, all of whom were infected with HCV. Two groups comprised patients who were infected with HIV as well as HCV, with either high or undetectable levels of HCV (30 patients in each group). The two other groups included patients not infected with HIV, either with high or undetectable levels of HCV (17 patients in each group). The researchers focused on the individuals who, despite coinfection with HIV, were able to control their HCV infection. They found that those individuals managed to maintain relatively high levels of CD4+ T cells that specifically recognize HCV. However, a quarter of these patients (six out of 25) failed to keep HCV levels down for the entire observation period of up to 2.5 years; their blood levels of HCV rose substantially, most likely due to recurrence of the previously suppressed virus (the researchers could not be certain that none of the patients had become infected again after a new exposure to HCV-contaminated blood, but there was no evidence that they had engaged in risky behavior). The rise of HCV levels in the blood of the relapsed patients coincided with a drop in overall CD4+ T cell numbers. Following relapse in these individuals, HCV did not return to undetectable levels during the study. During the same period none of the 16 HIV-uninfected people with controlled HCV infection experienced a recurrence of detectable HCV. Despite the relatively small numbers of patients, these results suggest that recurrence of HCV after initial control of the virus is more likely in people who are coinfected with HIV, and that HCV control is lost when CD4+ T cell counts fall. This is one more reason to test all HIV-positive patients for HCV coinfection. Coinfected patients, even those who seem to be controlling HCV and would not automatically receive HCV treatment, should be regularly tested for a rise of HCV levels. In addition, maintaining CD4+ T cells at a high level might be particularly important for those patients, which means that doctors might consider starting HAART therapy earlier than is generally recommended for HIV-infected individuals. Additional studies are needed to support these recommendations, however, especially as this study did not follow the patients long enough to determine the consequences of the observed loss of control of HCV. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030492. AIDS Treatment Data Network factsheet on HIV/HCV coinfection US CDC factsheet on HIV/HCV coinfection American Liver Foundation, information on HIV and HCV MedlinePlus pages on HCV
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影响因子：
13.5
作者：
Grebely, Jason;Conway, Brian;Tyndall, Mark W.
通讯作者：
Tyndall, Mark W.
影响因子：
5.4
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13.5
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影响因子：
29.4
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13.5
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通讯作者：
Chang, KM