Neuropsychiatric problems related to HIV infection and antiretroviral therapy in Cape Town

开普敦与艾滋病毒感染和抗逆转录病毒治疗相关的神经精神问题

• 批准号: MC_PC_MR/S008829/1
• 负责人: Saye Khoo
• 金额: $ 8.29万
• 依托单位: University of Liverpool
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_PC_MR%2FS008829%2F1
• 关键词: Neuropsychiatric; problems; related; HIV; infection

Neuropsychiatric problems are common in people living with HIV (PLWH). Cognitive impairment (ie. problems with thinking and memory) can affect around a quarter of PLWH and is often associated with depression and other mental health symptoms. These problems can have a major impact on the person involved, causing difficulties with daily functioning and decision-making, reduced employment and overall poorer quality of life. In addition, people with neuropsychiatric problems are less likely to take their HIV medication regularly, meaning that there is a risk that the treatment could become ineffective. PLWH who do not take their medication regularly (called poor adherence) are more likely to become unwell from HIV, and there is an increased risk they will pass the virus to someone else. In some PLWH neuropsychiatric problems can be related to damage to the brain, either from the HIV virus itself or from the antiretroviral medication taken to combat HIV. There is little known about the extent of this problem in South Africa, how to test for it and what to do to help those affected. This is an important area of research as these factors are potentially treatable. To investigate this we will perform a brief screening test for cognitive problems in Cape Town clinics. Based on this we will ask 178 people to be involved in our study - half with cognitive problems and half without. These will undergo more detailed neuropsychiatric profiling involving a computer based test of cognitive function and a series of questionnaires related to mental health symptoms. We will assess their adherence to medication by looking at how often they pick up their tablets and how much medication can be measured in their blood. We will then perform a lumbar puncture (LP); this involves putting a needle into the lower spine to take a sample of the fluid that sits around the brain and spinal cord, called cerebrospinal fluid or CSF. We will test the CSF to see if there is HIV virus at greater levels than in blood; this can occur in around 5-10% of patients and may be due to the lower concentrations of antiretroviral drugs found in the brain and CSF. It can cause inflammation to the brain and hence neuropsychiatric problems. We will then change their HIV treatment from efavirenz (current most common treatment in South Africa) to dolutegravir (a newer, more effective treatment). We will repeat testing and LP 6 months later. This will allow us to see to what extent HIV in the brain is causing neuropsychiatric problems, and whether dolutegravir is an effective treatment for this. Efavirenz can be toxic to the brain potentially leading to cognitive problems and/or depression. Although dolutegravir has fewer side effects it can also be toxic to the brain, causing anxiety and insomnia in some patients. As well as assessing symptoms we will measure drug concentrations in blood and CSF. This will allow us to investigate the toxic effects of these drugs on the brain. We will also test patients DNA to see whether genetic differences play a role in determining which patients are most affected. ODA compliance: The reason we are interested in these factors is that both HIV in the brain and drug toxicity can potentially be treated, offering a way to help PLWH with neuropsychiatric problems, and perhaps offer new ways to tackle poor adherence to medication. Such treatments would improve the welfare of PLWH and increase their potential to earn a living, support their family and contribute to society. Guidelines developed in Europe and North America suggest that PLWH should be routinely tested for cognitive impairment, and a LP performed if other causes have been excluded. We don't know whether this advice is appropriate for South Africa where the challenges are different and resources are more limited. This study will provide useful information to guide public health policy decisions in this area, ensuring funds are allocated most effectively.

神经精神问题在艾滋病毒感染者（PLWH）中很常见。认知障碍（即，思维和记忆问题）可以影响大约四分之一的PLWH，并且通常与抑郁症和其他心理健康症状有关。这些问题可能对有关人员产生重大影响，造成日常运作和决策困难，减少就业机会和总体生活质量下降。此外，有神经精神问题的人不太可能定期服用艾滋病毒药物，这意味着治疗可能无效。不定期服用药物的PLWH（称为依从性差）更有可能因艾滋病毒而感到不适，并且他们将病毒传播给他人的风险增加。在一些艾滋病毒携带者中，神经精神问题可能与大脑受损有关，无论是艾滋病毒本身还是对抗艾滋病毒的抗逆转录病毒药物。人们对南非这个问题的严重程度、如何进行检测以及如何帮助受影响的人知之甚少。这是一个重要的研究领域，因为这些因素是潜在的治疗。为了调查这一点，我们将在开普敦诊所进行一项简短的认知问题筛查测试。在此基础上，我们将邀请178人参与我们的研究-一半有认知问题，一半没有。这些将进行更详细的神经精神分析，包括基于计算机的认知功能测试和一系列与心理健康症状相关的问卷调查。我们将通过观察他们拿起药片的频率以及血液中可以测量到多少药物来评估他们对药物的依从性。然后，我们将进行腰椎穿刺（LP）;这涉及将针头插入下脊柱以获取位于大脑和脊髓周围的液体样本，称为脑脊液或CSF。我们将测试脑脊液，看看是否有HIV病毒在更高的水平比血液;这可能发生在大约5-10%的患者，可能是由于抗逆转录病毒药物在大脑和脑脊液中的浓度较低。它会导致大脑发炎，从而导致神经精神问题。然后，我们将把他们的艾滋病毒治疗从依法韦仑（目前南非最常见的治疗）改为度鲁特韦（一种更新，更有效的治疗）。我们将在6个月后重复测试和LP。这将使我们能够了解大脑中的HIV在多大程度上导致神经精神问题，以及度鲁特韦是否是一种有效的治疗方法。依法韦仑可能对大脑有毒，可能导致认知问题和/或抑郁症。虽然dolutegravir的副作用较少，但它也可能对大脑有毒，导致一些患者焦虑和失眠。除了评估症状外，我们还将测量血液和CSF中的药物浓度。这将使我们能够研究这些药物对大脑的毒性作用。我们还将测试患者的DNA，看看遗传差异是否在确定哪些患者受影响最大方面发挥作用。官方发展援助遵守情况：我们对这些因素感兴趣的原因是，大脑中的艾滋病毒和药物毒性都有可能被治疗，提供了一种帮助PLWH解决神经精神问题的方法，也许还提供了解决药物依从性差的新方法。这种治疗将改善艾滋病毒携带者的福利，并增加他们谋生、养家和为社会作出贡献的潜力。在欧洲和北美制定的指南建议PLWH应定期进行认知障碍测试，如果排除了其他原因，则进行LP。我们不知道这一建议是否适合南非，因为南非面临的挑战不同，资源更加有限。这项研究将提供有用的信息，以指导这一领域的公共卫生政策决策，确保资金得到最有效的分配。