HIV-1 DNA predicts disease progression and post-treatment virological control.
HIV-1 DNA predicts disease progression and post-treatment virological control.
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HIV-1 DNA预测疾病进展和治疗后病毒学控制。
DOI：
10.7554/elife.03821
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发表时间：
2014-09-12
期刊：
影响因子：
7.7
通讯作者：
SPARTACTrial Investigators
中科院分区：
文献类型：
--
作者：
Williams JP;Hurst J;Stöhr W;Robinson N;Brown H;Fisher M;Kinloch S;Cooper D;Schechter M;Tambussi G;Fidler S;Carrington M;Babiker A;Weber J;Koelsch KK;Kelleher AD;Phillips RE;Frater J;SPARTACTrial Investigators
在HIV-1感染中，尽管进行了抗逆转录病毒治疗（ART），但潜伏感染的细胞群仍有助于病毒持续存在。为了确定个体在ART可能会诱导一段时间的病毒血症控制停止治疗，我们假设，在原发性HIV-1感染（PHI）的潜伏感染细胞池的定量将预测临床进展和病毒复制后ART。我们测量了HIV-1 DNA在一个高度特征化的随机人群与PHI。我们探讨了HIV-1 DNA与临床进展的免疫学和病毒学标志物之间的关系，包括中断治疗的病毒反弹。在多变量分析中，HIV-1 DNA比血浆病毒载量更能预测疾病进展，并且在治疗中断时，可预测血浆病毒反弹的时间。HIV-1 DNA可能有助于识别在未来的HIV-1根除试验中可以安全中断ART的个体。临床试验注册：ISRCTN 76742797和EudraCT 2004 -000446-20 DOI：http://dx.doi.org/10.7554/eLife.03821.001 HIV是一种病毒，可以隐藏在和劫持免疫系统的细胞，并迫使它们产生新的病毒拷贝。这最终会破坏受感染的细胞，并削弱艾滋病毒感染者抵抗感染和疾病的能力。如果早期诊断和治疗，大多数艾滋病毒感染者现在都能长寿和健康，不会发展为艾滋病-艾滋病毒感染的最后阶段，以前无害的机会性感染可能会危及生命。然而，在研制出治疗艾滋病毒/艾滋病的方法之前，仍有许多障碍和挑战必须克服。使用抗逆转录病毒药物进行治疗可以将感染者血液中循环的艾滋病毒数量减少到无法检测到的水平。然而，当HIV感染细胞时，病毒会将其遗传物质的拷贝插入细胞的DNA中，对大多数患者来说，抗逆转录病毒治疗并不能解决这些“隐藏的病毒”。因此，尽管抗逆转录病毒药物有副作用，但必须终身服用，以防隐藏的病毒再次出现。随着对艾滋病毒/艾滋病治疗方法的研究势头越来越大，需要确定可能成为新的实验性治疗方法候选人的病人。虽然不建议作为标准临床护理的一部分，但测试患者的病毒水平是否会在没有药物的情况下保持抑制的唯一方法是在医生的密切监督下暂时停止治疗。因此，需要一种新的方法来确定是否有患者可能从停止抗逆转录病毒治疗中受益，更重要的是，那些可能不会受益的患者。威廉姆斯，赫斯特等人现在已经测试了直接测量HIV DNA的水平是否有助于预测病毒是否以及何时重新出现（或反弹）。在一组参与临床试验的HIV患者中，发现在治疗停止时HIV DNA水平较高的患者比HIV DNA水平较低的患者经历更快的病毒反弹。因此，这种方法可以识别出那些HIV病毒反弹风险最大的患者，因此如果他们的治疗中断，他们不太可能受益。威廉姆斯，赫斯特等人还发现，测量HIV DNA的水平可以帮助预测疾病在治疗和未治疗的患者中的进展情况。此外，这些预测比基于测量患者体内循环的病毒量的预测更准确。下一个挑战是确定其他方法来区分那些可能在一段时间内不接受治疗而保持“无病毒”的患者和那些不接受治疗的患者。有了这个目标，就有可能确定病毒为什么会复发的机制，从而开发出新的治疗方法来阻止这种情况的发生。这将使研制艾滋病毒/艾滋病的治疗方法成为一个更加切实的前景。DOI：http://dx.doi.org/10.7554/eLife.03821.002网站
In HIV-1 infection, a population of latently infected cells facilitates viral persistence despite antiretroviral therapy (ART). With the aim of identifying individuals in whom ART might induce a period of viraemic control on stopping therapy, we hypothesised that quantification of the pool of latently infected cells in primary HIV-1 infection (PHI) would predict clinical progression and viral replication following ART. We measured HIV-1 DNA in a highly characterised randomised population of individuals with PHI. We explored associations between HIV-1 DNA and immunological and virological markers of clinical progression, including viral rebound in those interrupting therapy. In multivariable analyses, HIV-1 DNA was more predictive of disease progression than plasma viral load and, at treatment interruption, predicted time to plasma virus rebound. HIV-1 DNA may help identify individuals who could safely interrupt ART in future HIV-1 eradication trials. Clinical trial registration: ISRCTN76742797 and EudraCT2004-000446-20 DOI: http://dx.doi.org/10.7554/eLife.03821.001 HIV is a virus that can hide in, and hijack, the cells of the immune system and force them to make new copies of the virus. This eventually destroys the infected cells and weakens the ability of a person with HIV to fight off infections and disease. If diagnosed early and treated, most people with HIV now live long and healthy lives and do not develop AIDS—the last stage of HIV infection when previously harmless, opportunistic infections can become life-threatening. However, there are still numerous hurdles and challenges that must be overcome before a cure for HIV/AIDS can be developed. Treatment with drugs called antiretrovirals can reduce the amount of the HIV virus circulating in an infected person's bloodstream to undetectable levels. However, when HIV infects a cell, the virus inserts a copy of its genetic material into the cell's DNA—and, for most patients, antiretroviral treatment does not tackle these ‘hidden viruses’. As such, and in spite of their side-effects, antiretroviral drugs have to be taken for life in case the hidden viruses re-emerge. As research into a cure for HIV/AIDS gathers momentum, patients who might be candidates for new experimental treatments will need to be identified. Although it is not recommended as part of standard clinical care, the only way to test if a patient's viral levels would remain suppressed without the drugs would be to temporarily stop the treatment under the close supervision of a physician. As such, a new method is needed to identify if there are patients who might benefit from stopping antiretroviral therapy, and more importantly, those who might not. Williams, Hurst et al. have now tested whether measuring the levels of HIV DNA directly might help to predict if, and when, the virus might re-emerge (or rebound). In a group of HIV patients participating in a clinical trial, those with higher levels of HIV DNA at the point that the treatment was stopped were found to experience faster viral rebound than those with lower levels of HIV DNA. This method could therefore identify those patients who are at the greatest risk of HIV viral rebound, and are therefore unlikely to benefit if their treatment is interrupted. Williams, Hurst et al. also found that measuring the levels of HIV DNA could help to predict how the disease would progress in treated and untreated patients. Furthermore, these predictions were more accurate than those based on measuring the amount of the virus circulating in a patient's body. The next challenge is to identify other methods to distinguish patients who may remain ‘virus-free’ for a period without treatment, from those who would not. With this achieved, it might be possible to identify the mechanisms that determine why the virus comes back and so develop new treatments to stop this happening. This would make developing a cure for HIV/AIDS a much more tangible prospect. DOI: http://dx.doi.org/10.7554/eLife.03821.002